Diabetes - Basic
science
Haemodynamics
The haemodynamics of the central retinal artery and central retinal vein seems to
be altered in patients with diabetic retinopathy. Colour Doppler imaging technique is a
useful method for assessing blood flow. Maximum blood velocity is significantly higher in
pre-retinopathy diabetic patients than in patients with non-proliferative diabetic
retinopathy in the central retinal artery and higher than both non-proliferative diabetic
retinopathy patients and also patients who previously received PRP for central retinal
vein thrombosis. The presence of systemic hypertension does not seem to influence the
blood flow velocity in any of these patients.
[Ophthalmology August 1996; 103:1245-1249]
Macular capillary blood flow is significantly reduced in diabetic maculopathy (without
clinically significant macular oedema) but does not seem to be related to the visual
acuity. The foveal avascular zone and the peri-foveal inter-capillary area are enlarged in
diabetic maculopathy with and without decreased visual acuity. However they are further
enlarged in patients with poorer visual acuity indicating an association of a critical
value of enlargement and a decline in the visual acuity. Visual acuity less than 20/20 is
consistent with FAZ and peri-foveal inter-capillary area size equal to or larger than 0.55
mm square and 14000 micrometer respectively.
[Archives of Ophthalmology May 1995; 113: 610-614]
Retinal hypoxia plays a major role in the pathogenesis of vascular and visual
dysfunction in diabetic patients. 100% oxygen breathing can reverse early contrast
sensitivity deficit in diabetics. Early vascular and visual dysfunction seem to be
reversible by hyperoxia.
[British Journal Ophthalmology March 1996; 80: 209-213]
Diabetes may be associated with blood-aqueous barrier breakdown, the breakdown may
precede the development of retinopathy, the more severe proliferative diabetic retinopathy
is associated with greater breakdown. Measuring the breakdown by the laser flare-cell
meter may be a valuable clinical method in detecting the onset and possible progression of
diabetic retinopathy.
[American Journal Ophthalmology June 1994; 117: 768-771]
It has been found that the ocular perfusion pressure is related to the incidence of
diabetic retinopathy, progression of the retinopathy and also to progression to
proliferative diabetic retinopathy in the younger onset groups but not in the older onset
groups whether or not taking insulin. Intraocular pressure and myopia do not seem to be
associated with any end point in any group, but in a covariate analysis myopia seems to be
protective against the development of proliferative diabetic retinopathy in younger onset
patient. These findings suggest a possible pressure phenomenon in relation to diabetic
retinopathy in younger onset patient and this would have implication on the treatment of
IOP and blood pressure
[Ophthalmology January 1994; 101: 77-83]
Ocular blood flow velocity (when measured with the colour Doppler method) is decreased
in diabetic patients with proliferative diabetic retinopathy when compared with controls
which suggest low retinal perfusion. Other previous studies reported both increased and
decreased blood flow in all stages of diabetic retinopathy. The issue of the retinal blood
flow velocity in diabetic patient has been controversial.
[British Journal Ophthalmology May 1995; 79: 413-416]
The dynamics of the aqueous humour does not seem to be affected to any clinically
significant degree by the presence of diabetes. However there is a tendency towards less
aqueous humour flow in advanced diabetic retinopathy.
[American Journal Ophthalmology September 1995; 120: 362-367]
The retinal haemodynamics seem to be altered in patients with long-standing diabetes.
Patients with short duration diabetes also have mildly increased total volumetric blood
flow rate. A statistically significant correction between the duration of diabetes and the
increased blood flow has also been observed. It is suggested that increased retinal blood
flow may play a role in the development of diabetic retinopathy.
[British Journal of Ophthalmology April 1996; 80: 327-331]
There are evidences that there is an intraocular Renin Angiotensin system independent
of that in the circulation. Intraocular synthesis of angiotensin II may be involved in the
blood supply and also in the pathogenesis of vascular processes e.g. neovascularisation in
diabetic retinopathy. Vitreous levels of pro-renin in diabetic patients is higher than
that in non-diabetic patients suggesting an activation of the Renin Angiotensin system in
diabetics.
[British Journal Ophthalmology February 1996, 80: 159-163]
The retinal micro-circulation is markedly different in diabetic patient from controls
even in the absence of cystoid macular oedema. The capillary blood velocity is
significantly reduced and the foveal avascular zone is significantly increased when
compared with healthy people. There is no significant difference in the capillary blood
velocity. Peri-foveal inter-capillary area and the foveal avascular zone in diabetic
patients whether there is cystoid macular oedema or not. This suggest that inner retinal
ischaemia plays no role in the in the pathogenesis of cystoid macular oedema formation in
diabetes.
[British Journal Ophthalmology July 1995; 79: 628-632]
Glycaemic control
Hyperglycaemia is a major cause for the development of diabetic retinopathy. Local
changes in the retinal capillaries are more prominent and more common than changes in the
cerebral capillaries. Local factors in the retina seem to play important role in the
development of diabetic retinopathy than factors in the cerebral capillaries.
[Archives of Ophthalmology March 1996; 114: 306-310]
Progression of diabetic retinopathy in human is difficult to control by strict
glycaemic control with intensive insulin treatment. Retinopathy can be induced (in dogs)
by intensive galactose rich diet. Galactose-induced retinopathy does not stop progressing
even after the cessation of the galactose diet. The vascular retinal lesions in diabetic
dogs may be due to sequelae of excessive tissue aldohexose that are not corrected by
correction of the aldohexose levels.
[Archives of Ophthalmology March 1995; 113: 355-358]
Long-term glycaemic control is significantly related to both development and
progression of retinopathy in patient with insulin dependent diabetes. Pre-puberty
duration of diabetes seems to be significant risk factor for the development of
retinopathy.
[Ophthalmology August 1993; 100: 1125-1130]
The cause of diabetic retinopathy is not understood. Many factors affect the natural
history of diabetic retinopathy. A longer duration of diabetes, higher glycosylated
haemoglobin (GHB) level and higher diastolic blood pressure are factors associated with an
increased risk of progression and a decreased chance of regression of diabetic
retinopathy. Cigarette smoking is only associated significantly with background
retinopathy while systolic blood pressure, sex, family history of hypertension and
cholesterol level were not associated with retinopathy
[Ophthalmology August 1993; 100: 1133-1139]
Some patient show progression of their diabetic retinopathy shortly after the
institution of strict diabetic control. Institution of strict diabetic control results in
a significant increase in blood flow of the macula and the retinal circulation. Increase
in the macular blood flow may play a role in the progression of diabetic maculopathy.
[British Journal Ophthalmology August 1995; 119: 735-741]
A 10 mm Hg or more increase in the systolic blood pressure is associated with an
increased incidence of diabetic retinopathy in younger onset diabetic patients 10 years
after base line examination. No such association is found in adult onset diabetics.
[Archives of Ophthalmology May 1995; 113: 601-606]
There is strong evidence suggesting that there is a strong relation between
hyperglycaemia and the increased incidence of diabetic retinopathy. Normalisation of blood
sugar level (associated with a combined kidney-pancreas transplantation in patients with
proliferative diabetic retinopathy) does not seem to have a beneficial effect on the
progression of advanced diabetic retinopathy.
[Ophthalmology June 1994; 101: 1071-1076]
Several factors have been implicated in the mechanism(s) of diabetic retinopathy. These
include non-enzymatic glycation, free radical damage, aldose reductase induction, and
myoinositol depletion. However, it is clear from the Diabetes Control and Complication
Trials that a clear correlation exists between glucose control and susceptibility to the
complications of diabetes. High ambient glucose levels have been shown to alter second
messenger generation in astrocytes. The high concentrations of glucose that are reached in
diabetes mellitus can stimulate the transcription of genes coding for growth factors.
Growth factors may also influence the progression of diabetic complications by altering
the innate glucose regulatory mechanisms of the retina. Monocytes have been shown to be
associated with micro-aneurysms in the retinas of rats with alloxan induced diabetes.
Mononuclear cells may be dysfunctional at the level of their glucose regulatory
mechanisms. Thus, circulatory and localised effects must be considered in an overall
discussion of the mechanisms of the complications of diabetes.
[British Journal of Ophthalmology November 1995; 79: 1046-1049]
Data show that in young IDDM patients, the relative risk of proliferative diabetic
retinopathy developing in patients with gross proteinuria is 2.32 compared to those
without proteinuria, for those patients not taking insulin, the relative risk is 1.13.
[Ophthalmology August 1993; 100: 1140-1146]
Micro-albuminuria (between 0.03 and 0.29 g/l) is associated with greater risk of
developing clinical diabetic nephropathy and cardiovascular complications from diabetes.
Micro-albuminuria is associated with the presence of retinopathy in diabetic patients and
also with the presence of proliferative diabetic retinopathy in younger onset patients.
Micro-albuminuria may be a marker for the development of proliferative diabetic
retinopathy in younger onset patients. It remain to be determined whether
micro-albuminuria is a good marker for the risk of developing diabetic retinopathy in
general.
[Ophthalmology June 1993; 100: 862-867]
The vascular endothelial
growth factor (VEGF)
The nature of the angiogenic growth factor that stimulate retinal
neovascularisation in under-perfused diabetic retina is not exactly known. In retinal
ischaemia, the production of Vascular Endothelial Growth Factor (VEGF) is regulated in
response to the levels of retinal hypoxia. VEGF immune-reactivity is increased in the
diabetic retina and choroid suggesting that it may contribute to increased vascular
permeability and angiogenesis.
[Archives of Ophthalmology August 1996; 114: 971-977]
Vascular endothelial growth factor (VEGF) is a hypoxia-induced angiogenic factor that
has been shown to increased in the vitreous of diabetic patients with proliferative
diabetic retinopathy. The VEGF seems to up-regulated by the neuro-sensory retina in
diabetics with proliferative diabetic retinopathy. VEGF may be the link factor between
ischaemia and proliferative diabetic retinopathy associated neovascularisation.
[British Journal Ophthalmology March 1996; 80: 241-245]
Vascular endothelial growth factor (VEGF) is an endothelial cells specific mitogenic,
angiogenic protein and potent vaso-permeability factor. Hypoxia increases VEGF levels in
all retinal cell types which promotes retinal endothelial cells proliferation. VEGF levels
can be normalised by return to normal oxygen levels. These findings suggest that VEGF
plays a major role in mediating intraocular neovascularisation in ischaemic conditions.
[Archives of Ophthalmology December 1995,113: 1538-1544]
In proliferative diabetic retinopathy vascular endothelial cell growth (VEGF) control
is lost resulting in severe tissue injury and possible blindness. Retinal ischaemia
precedes the onset of retinal and iris vascularization and ischaemic retina has been
identified as a source of diffusable angiogenic factors. The vitreous levels of vascular
endothelial growth factors is significantly higher in patient with proliferative diabetic
retinopathy than in eyes without proliferative diabetic retinopathy. Data indicate that
the vascular endothelial factor (also called permeability factor) seems to play an
important role in the pathogenesis of proliferative diabetic retinopathy.
[American Journal of Ophthalmology October 1994; 118: 445-450]
The pathogenesis of diabetic retinopathy is not yet well established. It is thought
that retinal factors are responsible for the development of the retinal vascular disease.
Vascular endothelial growth factor (VEGF) appears to be the most likely factor responsible
for the development of diabetic retinopathy. VEGF is a heparin binding protein with
molecular weight of about 46kd. Vascular endothelial growth factor is the only factor that
is always expressed in samples of neovascular membranes taken from diabetic patients.
Vascular endothelial growth factor receptors-binding activity is also greater in the
vitreous samples taken from diabetic patients than in samples taken from controls.
[Archives of Ophthalmology November 1994; 112: 1476-1482]
Insulin-like growth factor 1 (IGF-1) stimulates the growth, differentiation and
metabolism of a variety of cells. It may have a role in the development of human retina.
All the three retinal cell types seem to be capable of producing both IGF-1 and cell
specific IGFBP in vitro. It is shown that the IGF-1 and its associated binding proteins
may have an autocrine / paracrine function and may also play a role in retinal physiology
and retinal disease.
[British Journal of Ophthalmology August 1994; 78: 638-642]
Growth factors are likely to be involved in the pathogenesis of PDR. It is not clear
whether these growth factors originate from the pathological tissues and thus act in a
paracrine / autocrine fashion or whether they originate from other local or systemic
sources. Immune- staining studies of epidermal and transforming growth factors and their
receptors is much greater in retina with PDR compared to normal indicating that they have
an autocrine/paracrine role.
[British Journal of Ophthalmology September 1994; 78: 714-718]
Other considerations
There is an experimental evidence to support the theory that retinal pigment
epithelium plays an important role in the development of diabetic macular oedema even in
eyes with minimal diabetic retinopathy and no clinically significant macular oedema. The
retinal blood vessels seem to be not the only source of extra-cellular fluid. Diabetic
retinal epitheliopathy is associated with break down of the outer blood-retinal barriers
which lead to leakage through the retinal pigment epithelium.
[British Journal of Ophthalmology August 1995; 79: 728-731]
Both C57BL/6 and BALB/C mice can provide a suitable and inexpensive model for diabetic
retinopathy after being fed galactose-rich diets. These mice may provide a good model in
vitro study of the pathogenesis of diabetic retinopathy. Mice genetics are well understood
(unlike dogs and cats) and can be manipulated by genetic engineering methods.
[Archives of Ophthalmology August 1996; 114: 986-990]
Local deposition of the cytokines tumour necrosis factor alpha (TNF alpha) and its
vascular adhesions molecules may be an important factor in the pathogenesis of
proliferative diabetic retinopathy.
[British Journal Ophthalmology February 1996; 80: 168-173]
Galactose fed dogs can be used as animal models that can develop diabetic like vascular
changes. This model can be used in the study of effects of various factors e.g. the
glycaemic blood level on the incidence and progression of retinopathy.
[Archives of Ophthalmology March 1995; 113: 352-354]
Diabetic retinopathy rarely occurs before puberty suggesting that sex hormones may a
role in its pathogenesis. Neither serum testosterone nor other sex hormones are related to
the incidence of severe retinopathy, however sex hormone-binding globulins are
significantly lower in patients than in controls indicating that increased androgenecity
may be associated with progression of retinopathy in male subjects with type 1 diabetes.
[Ophthalmology December 1993; 100: 1782-1786]
There is an increase in the lens auto-fluorescence in the adolescent diabetic patients
compared with controls, that increase is striking and shows a significant positive
correlation with the duration of diabetes. The permeability of the blood aqueous barrier
is also increased in the adolescent diabetic patients compared with the controls and shows
a significant positive correlation with the glycohaemoglobin levels. No significant
differences from the controls were observed regarding the permeability of the blood
retinal barrier. In the adult group there is no significant difference in either the
permeability of the blood-retina barrier or the blood-aqueous barrier between the
diabetics and the controlled groups. These findings suggest that in the adolescent
diabetic patients, the blood aqueous barrier permeability increased before an onset of
retinopathy suggesting that this is the cause of striking increased lens
auto-fluorescence.
[British Journal of Ophthalmology March 1993; 77: 158-161]
Histopathology
Thickening of the retinal capillary basement membrane is well documented in
patients with diabetes. Basement membrane of the retinal capillaries are thicker in
arterial environments of the retina than in venous environments. Capillaries in the nerve
fibre layer also seem to have thicker Basement membrane than in the inner or outer
plexiform layers. This difference may be due to different level of oxygen tension and
oxidative stress in the retina around the arteries compared with that around the veins.
[British Journal of Ophthalmology December 1995; 79: 1120-1123]
Smooth muscle cell loss (a previously unknown feature of diabetes) accompanies pericyte
cells loss in the retinal circulation in dogs (good model for human diabetes). The smooth
muscle cell loss paralleled the loss of pericyte and appeared 4 years after the onset of
diabetes, micro-aneurysms did not appear till 7 years after the diabetes, it may be that
the cell loss resulted in weakening of the vessel wall which resulted later in the
formation of micro-aneurysms.
[British Journal Ophthalmology January 1994,78: 54-60]
Human retinal blood vessels are characterised by non-fenestrated continuos endothelial
cells with tight intercellular junctions (blood-retinal barrier). Retinal vessels in
diabetic patients are characterised by having thin endothelial cytoplasm with
trans-cytoplasmic channels and endothelial fenestration. These morphological changes may
account for the characteristic break down in the blood-retinal barriers in diabetic
patient. The tight junctions between the endothelial cells seem to be rarely altered.
[British Journal of Ophthalmology September 1993; 77: 574-578]
Basement membrane thickening is thought to be the most major and the earliest abnormal
characteristic of Diabetic Micro Angiopathy, not only in the retina but also in the
kidney, muscle and the skin of human beings and animals. Data show that the basement
membrane of the retinal capillaries from the diabetic dogs are significantly thicker than
those from controlled dogs. Furthermore within the diabetic dogs the arterial environment
capillaries have thicker basement membranes than the venous environment capillaries. It is
concluded that the diabetic capillaries are more vulnerable to basement membrane
thickening in an arterial environment than in a venous one. This difference may result
from a complex interplay between hyperglycaemia and the enhancing oxidation in he arterial
size of the capillaries.
[British Journal of Ophthalmology February 1994; 78: 133-137]
The intravitreal membranes of proliferative diabetic retinopathy contain a variety of
cell types. Retinal pigment epithelial cells seems to contribute to combined
rhegmatogenous and traction retinal detachment rather than traction retinal detachment
membranes alone. Presumably, the detachment starts as a typical fibrovascular traction
retinal detachment which may cause a retinal tear and subsequently migration and
proliferation of the retinal pigment epithelium. The late acquisition of the retinal
pigment epithelium cells seems to give a combined rhegmatogenous traction membranes and
proliferative vitreoretinopathy membranes.
[British Journal of Ophthalmology March 1994; 78: 219-222]
Visual pathway function is abnormal in patients with insulin dependent diabetes even in
the absence of diabetic retinopathy. The mechanism underlying this abnormality is unknown.
The presence of some visual pathway dysfunction in some insulin dependent diabetes
patients within weeks of diagnosis and failure to find a correlation between the
dysfunction and the duration of the diabetes suggest that the pathway dysfunction may not
be a micro-vascular complications, it may be a result of a reversible changes in the
retinal function perhaps secondary to a metabolic abnormality of the diabetes leading to
tissue hypoxia. It has been hypothesised that short term changes in the blood glucose
level may affect the visual pathway function in diabetic patients. Short term (between 1
and 2 hours) changes in the blood glucose level seem to be not directly related to the
visual pathway dysfunction in the patients without diabetic retinopathy. Short term
changes in the blood glucose level does nor affect colour discrimination 100-hue test in
insulin dependent diabetic patients without diabetic retinopathy.
[British Journal of Ophthalmology January 1995; 79: 38-41]
The mechanism of the development of diabetic epiretinal membranes is still unknown. The
expression of cell adhesion molecules, especially ICAM-1 and VCAM-1 in diabetic epiretinal
membranes suggests that cell to cell interactions may play a significant role in the
development of proliferative diabetic retinopathy membranes. The expression of ICAM-1 and
VCAM-1 on proliferating endothelial cells indicates the activation of these cells (which
is the first critical step for lymphocyte/endothelial cell interactions and the initiation
of immune responses). The proliferating status of the neovascular membrane may reflect the
course and the prognosis of the disease. Pharmacological treatment may prove to be another
choice in the treatment of diabetic membranes.
[British Journal of Ophthalmology May 1994; 78: 370-376]
Macrophages seem to play an important role in the pathogenesis of proliferative
vitreoretinopathy, they seem to be predominantly dominant in traumatic proliferative
vitreoretinopathy and proliferative diabetic retinopathy. All types of macrophages can be
detected regardless the duration and the clinical history. In traumatic proliferative
vitreoretinopathy inflammatory macrophages seem to be more associated with short history
of the disease.
[British Journal of Ophthalmology November 1993; 77: 731-733]
Diabetic Retinopathy - Screening
Proliferative diabetic retinopathy is more likely to develop in younger
onset diabetic women with less education than in those with more education, no relation to
the level of education is found in the older onset group. Education seems to be associated
inversely with the incidence of visual loss in younger onset women and older onset men.
The relationship between the socio-economic factors and other diseases have been
attributed to poor nutrition, poor medical care and also to been exposed to adverse home
and work environment.
[Ophthalmology January 1994,101: 68-76]
The 10-year incidence and progression of diabetic retinopathy and the rate of
progression of the retinopathy and progression to proliferative retinopathy is high in
young diabetics (diagnosed before the age of 30 years old), moderate in insulin dependent
patients diagnosed at the age of 30 years old or older, and low in the non-insulin
dependent diabetics.
[Archives of Ophthalmology September 1994; 112: 1217-1228]
It is accepted that the development of diabetic retinopathy is related to the duration
of diabetes and that puberty plays a part in the progression of the disease. The blood
retinal barrier appears to remain stable until puberty and progressively declines
afterwards. There seems to be an association between puberty, decline of the blood retinal
barrier and the development of diabetic retinopathy. The role of hormones and
endocrinology in the development of diabetic retinopathy is not exactly known.
[Archives of Ophthalmology October 1994,112: 1334-1338]
The ratio 30:15 (which is the ratio between the variation in the heart rate at the 30th
beat to the heart rate at the 15th beat) is lower than normal in patient with
proliferative diabetic retinopathy. Cardiovascular autonomic neuropathy seems to be
associated with an increased risk of the development of proliferative diabetic
retinopathy. The risk of developing proliferative diabetic retinopathy in patient with
abnormal autonomic cardiovascular neuropathy is about 2.59. Non-ocular causes, as well as
ocular causes, seem to be important in evaluating diabetic patient with diabetic
retinopathy.
[American Journal Ophthalmology September 1995; 120: 317-321]
Physical activities are associated with a decreased risk of mortality and
macro-vascular complications in patients with diabetes. Physical activities does not
appear to have any positive or negative effect on the progression of diabetic retinopathy
or the development of proliferative diabetic retinopathy in patients with insulin
dependent diabetes.
[Ophthalmology August 1995; 102: 1177-1182]
Hypoxia is an important factor in the progression of diabetic retinopathy. Smoking may
have a detrimental effect which may be compounded further by the additional effects
smoking has on auto-regulation. Two important constituents of cigarette smoke can affect
the circulation, nicotine and carbon monoxide. Nicotine (by stimulating both the
sympathetic ganglion and adrenal glands) leads to sympathetic over-activity that may have
a harmful effect on the blood flow. The affinity of haemoglobin to carbon monoxide is far
greater than it is for oxygen, therefore reducing the capacity of the blood to carry and
deliver oxygen, (this may also have an effect on the blood flow). Smoking reduces retinal
blood flow and the ability of the retinal blood vessels to auto-regulate to hyperoxia.
These effects are likely to be due to the vasoconstrictor effect of nicotine. Smoking also
increases the level of carboxyhaemoglobin thereby reducing the oxygen carrying capacity of
the blood which when associated with reduced blood flow may reduce the retinal oxygen
delivery.
[Ophthalmology July 1994; 101: 1220-1226]
Cigarette smoking does not seem to be a risk factor for the incidence of diabetic
retinopathy. However, cigarettes are associated with increased incidence of cardiovascular
system complications and cancer formation.
[Ophthalmology September 1996; 103:1438-1442]
Patients with advanced diabetic eye disease are commonly in poor general health. The
five years survival rate is about 68% in diabetic patients needing vitrectomy. Absence of
heart disease is the most important predicting factor for survival. 58% of patients with
heart disease die within 3.5 years. Patients without hear disease have a five year
survival rate of 90%. other significant factors for survival are age and the presence of
nephropathy. These factors should be taken in consideration for treatment strategies in
patients with diabetic retinopathy.
[British Journal of Ophthalmology July 1996; 80: 640-643]
It seems that more aggressive intervention for improving eye care is needed for
diabetic patients among American patients. A large percentage of elderly people with
diabetes is not receiving the necessary eye care especially blacks, men and those living
in poor areas with fewer Ophthalmologists. There is no association between eye care use
and regional educational level and optometrists supply.
[Ophthalmology November 1996; 103:1744-1750]
Pregnancy can adversely affect the natural course of diabetic retinopathy. Reported
cases of new cases or progression of existing cases ranges from 16-85%. Regression of some
of the non-proliferative changes after delivery has also been reported. Progression of
diabetic retinopathy in pregnant women seems to be associated with a longer period of
diabetes, higher levels of glycohaemoglobin levels and also lower levels of haemoglobin.
Systolic blood pressure is also higher in patients who show signs of progression.
[Ophthalmology November 1996; 103:1815-1819]
Several risk factors are associated with loss of vision in diabetic patients over a ten
year period. The presence of macular oedema or more severe retinopathy is associated with
visual loss. Visual loss seems to be associated with smoking (in the young onset
diabetics) and with systolic blood pressure (in older onset diabetics taking insulin). The
incidence of blindness in younger onset diabetics, older onset insulin dependant diabetics
and older onset non-insulin dependant diabetics are 1.8%, 4.0% and 4.8%. The incidence of
blindness seems to be decreasing.
[Ophthalmology June 1994; 101: 1061-1070]
Screening and Epidemiology
Screening for diabetic retinopathy reduces the risk of blindness in diabetic
patients by 50%. Fundus photography has been successfully tried but it needs an expert
Ophthalmologist to examine the photographs. Conventional digital image analysis is made
difficult by the inherent variability of fundi. Fundus photos can be stored on Computer
and analysed by neural network which has been trained to recognise features in the retinal
images. When compared with Ophthalmologists, the neural network achieves a sensitivity of
88.4% and specificity of 83.5% for the detection of diabetic retinopathy. The success rate
of this technique depends on pre-processing of images and the number of images used in
training.
[British Journal of Ophthalmology November 1996; 80: 940-944]
Screening programs for diabetic retinopathy are proved to be cost effective. There is
no agreement on the best method of screening for diabetic retinopathy. Ophthalmic
Opticians with suitable training appear to be suitable to screen diabetic patients for
diabetic retinopathy. In comparison with Ophthalmologists, Ophthalmic Opticians tend to
diagnose less BGDR and diabetic maculopathy.
[EYE (1996) 10, 107-112]
Regular screening for back ground diabetic retinopathy, proliferative diabetic
retinopathy and diabetic macular oedema is needed in diabetic patients. When screening
sensitivity is higher (e.g. by expert Ophthalmologists) the frequency of screening makes
little difference to the years of sight saved, but when sensitivities are close to 50% the
frequency of examination is an important factor. Biannual, (rather than annual) screening
may be considered when the screening sensitivity is high.
[British Journal of Ophthalmology November 1996; 80: 945- 950]
The benefit of screening for diabetic retinopathy is well established. 50% of patients
registered blind in this study in Avon were not screened before referral to the hospital,
however 25% of the registered patients had screening which failed to identify the serious
diabetic retinopathy and 22% of patients were newly diagnosed only when referred to the
hospital. 72% of registered patients had diabetic macular oedema. delay in referral to the
hospital does not seem to contribute to the final outcome of visual acuity.
[British Journal of Ophthalmology October 1994; 78: 741-744]
Fundus photography with non-mydriatic cameras in dilated eyes is comparable to fundus
ophthalmoscopy for the detection of diabetic retinopathy. This method may prove to useful
and cost effective in screening patient in diabetic clinics. Ophthalmic referral is
needed, however, in those patient with suspected retinopathy and in cases of poor
photographs.
[Ophthalmology October 1993; 100: 1504-1512]
Epidemiological studies demonstrated a negative risk factor for the development of
diabetic retinopathy with myopia higher than 5 dioptres. This is probably due to the poor
blood supply of the myopic retina or due the retinal thinning in these cases. in eyes with
tilted discs this relative protective effect has been noticed in the staphylomatous areas
of the retina.
[Archives Ophthalmology February 1996,114: 230-231]
Screening for diabetic retinopathy is important. Screening may be carried out by
clinical examination, by examining fundus photos or by examining patient suspected of
having diabetic retinopathy on the basis of fundus photos of the disc and the macula. In a
population of diabetics and non-diabetics clinical examination by an ophthalmologist would
detect most cases of diabetic retinopathy identified by disc and retinal photos. The
prevalence of diabetic retinopathy seems to be higher when screening is carried out by
photos and clinical examination than by either method alone.
[Archives of Ophthalmology August 1993; 111: 1064-1070]
This report deals with ocular examination in all population of known no-insulin
diabetic pat in an English town. The overall prevalence of diabetic retinopathy in this
population was estimated o be 52%, 4% for proliferative diabetic retinopathy, and 10% for
maculopathy needing treatment. Risk factors, identified in this study, for the development
of diabetic retinopathy include longer diabetic duration, female sex, higher blood
pressure, smoking and the use of anti-hypertensive medications. The visual acuity in 76%
of patient was estimated to be 6/12 or better.
[Eye (1993) 7; 158-163]
# $ K
Methods of
Examination
Fluorescein angiography
Iris fluorescein angiography in diabetic patients is useful in demonstrating iris
neovascular vessels and to guide laser treatment. However, fluorescein angiography fails
to demonstrate iris new vessels in heavy pigmented iris. Capillary dilatation and iris
hypo-perfusion are better identified by Indocyanine green angiography while iris new
vessels seem to be better detected by fluorescein angiography. There does not seem to be
any relation between iris capillary dilatation or iris hypo-perfusion and the degree of
diabetic retinopathy.
[British Journal of Ophthalmology May 1996; 80: 416-419]
Retinal assessment may not be possible in diabetic patients with unclear media. The
presence of diabetic retinopathy might contraindicate some ocular operations because of
the likely high level of complications. Iris fluorescein angiography gives valuable
information about the status of the diabetic retinopathy and may be helpful in avoiding
complications when considering ocular surgery in diabetic patients. In pre-proliferative
and proliferative diabetic retinopathy iris fluorescein angiography have a sensitivity of
56% and specificity of 100% in detecting the diabetic retinopathy changes. Its positive
prediction value is 100% and its negative prediction value is 65%. The absence of iris
changes does not, however, role out the presence of diabetic retinopathy.
[British Journal of Ophthalmology July 1994; 78: 542-545]
The scanning laser ophthalmoscopy
The scanning laser ophthalmoscopy uses a focused laser beam which is directed in a
roster format across the retina, the reflected light is gathered and displayed on a video
monitor, it provides a higher resolution image with lower level of illumination than in
the conventional ophthalmoscopy. The scanning laser ophthalmoscopy is not very good in
detecting cotton wool spots and subtle IRMA but it does not seem to miss any new-vessels
in diabetics with non-mydriatic examination.
[Eye (1994) 8; 437-439]
Fundus photography
The Nidek 3DX Camera has certain advantages over the conventional fundus camera
including the ability to take simultaneous photos that constitute a stereo pair of photos
with a single exposure. Nidek 3DX Camera seems to be suitable for photographic detection
of significant diabetic macular oedema and may have potential advantages over a
conventional camera by achieving good quality gradable stereo-graphs in the majority of
eyes. The camera has also been used for optic disc photography in glaucoma patients and
provides good quality images of the optic nerve measurements. This technique may become a
good screening method for detecting diabetic macular oedema.
[American Journal of Ophthalmology November 1996; 122: 654-662]
Electrophysiology
Diabetic patients with or without retinopathy show a selective reduction of the S
cone ERG which is believed to reflect changes in the outer retina. Previous reports
indicate that the sensitivity loss of the S cone may precede ophthalmic retinal changes.
The S cone ERG may prove to be a useful indicator of diabetic retinopathy development.
[British Journal of Ophthalmology November 1996; 80: 973-975]
Optical coherence tomography
Optical coherence tomography is a new technique for high resolution cross section
retinal imaging that is analogous to ultrasound except that it uses optical rather that
sound waves to provide much higher resolution than the us. Optical coherence tomography is
a useful method of monitoring macular oedema and retinal thickness and may prove in the
future to be a sensitive test for the early detection of macular thickness in patient with
diabetic retinopathy. It has been shown to be more sensitive than the scanning laser in
detecting an early diabetic retinopathy and also to be correlated with the visual acuity
in patient with diabetic macular oedema
[Archives of Ophthalmology August 1995; 113: 1019-1029]
Colour vision
Colour discrimination performance (100- hue test) has been compared to ERG for the
detection of visual abnormalities in patients with insulin diabetes. The 100-hue test
seems to be more sensitive and more specific than ERG in the detection of diabetic visual
dysfunction. Colour discrimination method by the 100-hue test appear to be more useful
than ERG oscillatory potential implicit time in the evaluation of the visual pathway
dysfunction in diabetic patients without diabetic retinopathy. Not only that it is more
sensitive and relatively more specific than ERG but it is also quicker, less invasive,
cheaper and needs less technical support than the ERG.
[British Journal of Ophthalmology January 1995; 79: 35-37]
Colour discrimination is abnormal in patients with diabetes even in the absence of
diabetic retinopathy. Colour discrimination abnormalities seem to be the result of a
functional disturbance in the retina and can not be completely explained only on the basis
of diabetes induced increase in the lens optical density.
[British Journal of Ophthalmology October 1994; 78: 754-756]
Laser flare meter
Laser flare intensity correlates with the duration of diabetes and also with the
actual aqueous protein concentration. There is a significant increase in the flare
intensity after 6 decades of diabetes and also in all patients with proliferative diabetic
retinopathy. The precise value of laser flare intensity may be a new indicator to evaluate
diabetic changes in the blood-aqueous barrier.
[British Journal of Ophthalmology September 1994; 78: 694-697]
Pupil dilatation
Full pupillary dilatation is needed to examine patients with diabetic retinopathy.
A comparison between two different methods of pupillary dilatation using either
Tropicamide Novel Ophthalmic Delivery System (NODS) and a combined preparation of
phenylephrine and Tropicamide eye drops showed no statistical difference between the two
systems thirty minutes after the instillation of the drops. The combined eye drops system,
seems to work faster than the Tropicamide (NODS) preparation. Tropicamide NODS costs about
17.7p compared with 29.5p for one minims of either phenylephrine or Tropicamide eye drops.
[EYE (1995);9: 811-812]
#
$ K
Clinical Features
Methods of Examination Background diabetic retinopathy
and macular oedema
Background diabetic
retinopathy and macular oedema
Increase in the number of retinal micro-aneurysms or in the ratio of the number of
retinal micro-aneurysms to the base line number is positively associated with the
incidence of proliferative diabetic retinopathy and clinically significant macular oedema.
Micro-aneurysms count may be used as an indicator of diabetic retinopathy progression.
[Archives of Ophthalmology November 1995; 113: 1386-1391]
Four different types of micro-aneurysms are recognised in patients with diabetic
retinopathy, 1. Micro-aneurysms with polymorphonuclear cells in the lumen with intact
endothelium and absent pericytes, 2. Micro-aneurysms with red blood cells in the lumen
with absent endothelium and pericytes, 3. Micro-aneurysms with irregular shaped red blood
cells and red blood cells breakdown products with or without re-canalisation of its lumen,
4. Sclerosed micro-aneurysms with extensive fibrosis and lipid infiltration in the lumen
and basement membrane. Pericytes loss appear to be critical in the development of
micro-aneurysms and diabetic retinopathy.
[British Journal of Ophthalmology April 1995; 79; 362-367]
Background diabetic retinopathy is a dynamic process. About 50% of the micro-aneurysms
disappear within two years with new micro-aneurysms appearing with a net result of slight
increase. Micro-aneurysms disappearance and formation may be a more sensitive indicator of
the progression of diabetic retinopathy than the micro-aneurysms count changes.
[British Journal Ophthalmology January 1996; 80: 135-139]
Vitreous abnormalities may play a role in some cases with diabetic macular oedema. Eyes
with diabetic retinopathy are more likely to develop macular oedema if the posterior
hyaloid membrane is attached to the macula. Vitrectomy and removal of the posterior
hyaloid membrane may result in reduced macular oedema and improved visual acuity after
laser photocoagulation. It is important, but not often easy, to assess any macular
traction from an attached, thickened, or taut posterior hyaloid membrane in assessing
diabetic macular oedema as in some of these cases vitrectomy may be associated with
improved visual results.
[American Journal Ophthalmology April 1996; 121: 405-413]
Focal laser photocoagulation should be considered for patients with clinically
significant macular oedema when the centre of the macula is involved or threatened. In
eyes with less extensive retinal thickening and less thickening of the centre of the
macula close observation may be preferred to immediate laser treatment especially when
most of the fluorescein leakage arise close to the centre of the macula which might
increase the risk of macular damage due to migration of the treatment scars. The presence
of cystoid macular oedema does not seem to have a prognostic importance on the effect of
the treatment.
[Archives of Ophthalmology September 1995; 113: 1144-1155]
Macular oedema in the younger onset diabetics over a 10 years period is estimated to be
20.1%and 25.4% in the older onset patient taking insulin and 13.9% in non-insulin patient.
Reduction in hyperglycaemia may result in reduction in the incidence of the macular
oedema.
[Ophthalmology January 1995; 102: 7-16]
Proliferative diabetic retinopathy
Spontaneous regression of new vessels in proliferative diabetic retinopathy may
rarely occur. This spontaneous regression does not seem to be related to any improvement
in the diabetic control. The regression seems to be associated with improvement in the
blood-retinal barrier breakdown as measured by fluorescein angiography.
[American Journal of Ophthalmology October 1996; 122: 494-501]
Angle neovascularisation may lead to neovascular glaucoma in patient with diabetes and
central retinal vein occlusion. In diabetic patients screening gonioscopy examination is
valuable in early detection of iris neovascularisation as iris new vessels occasionally
develop in the angle before the pupil margin. Other ophthalmologists believe that a good
alit lamp examination of the pupil margin is simply enough
[American Journal of Ophthalmology September 1995; 120: 393-394]
Proliferative Diabetic Retinopathy characteristically assumes an oval, ring or C-shaped
configuration with its opening temporal to the macula. The fibrovascular tissue tends to
form along the temporal vascular arcade but it may develop out of the arcades or temporal
to the macula where the vascular arcade is absent. This paper showed that posterior
vitreous detachment was prevalent outer to the ring shaped proliferation and that in the
posterior fundus inner to the ring, only the gel component of the vitreous was detached
from fundus with the cortical vitreous still attached onto the retina. The profile of this
pocket became obvious when the vitreous haemorrhage settled within the posterior
pre-cortical vitreous pocket. The ring shape proliferation was formed along its outer
margin. These results suggest that a posterior pre-cortical vitreous pocket which is a
physiologically presented premacular liquefied lacuna of the vitreous is a key role in
determining the pattern of proliferation in some types of diabetic retinopathy.
[Ophthalmology February 1993; 100: 225-229]
In pre-proliferative diabetic retinopathy and proliferative diabetic retinopathy, areas
of capillary non perfusion are closely associated with areas of reduced retinal
sensitivity and visual field defects. More severe visual field defects are found in
non-insulin dependant diabetics and also in older patients.
[British Journal of Ophthalmology November 1993, 77: 726-730]
Diabetic retinopathy with severe equatorial fibrovascular proliferation (resulting in
traction, or traction rhegmatogenous detachment, vitreous haemorrhage and hypotony)
appears to be a distinct entity. Patients need vitrectomy with adequate dissection of the
fibrovascular tissues and also scleral buckling to relieve the retinal traction. In
advanced cases lensectomy with or without relaxing retinotomy may also be needed.
[American Journal of Ophthalmology May 1995; 119: 563-570]
Rubeosis irides may develop rapidly in eyes with non-proliferative diabetic retinopathy
in patients with IDDM or NIDDM after ECCE with posterior camber IOL despite good diabetes
control. Rubeosis may also be associated with rapid and severe visual deterioration. In
diabetic patients, follow up after ECCE should be carried out with special consideration
to the diabetic retinopathy and post-operative checks should be at short intervals.
[EYE (1995) 9; 728-732]
In proliferative diabetic retinopathy additional epiretinal membranes have been
described. These membranes are thought to represent the posterior layer of a split
posterior vitreous cortex. The anterior and the posterior layers of the split posterior
vitreous cortex are attached at fibrovascular portions of the epiretinal membrane. The
identification and recognition of these anatomical landmarks is important in vitrectomy
and delamination procedures in diabetic patients with traction retinal detachment.
[Ophthalmology February 1996; 103: 323-328]
A case of vitreous haemorrhage noticed immediately in a diabetic patient after
treatment with hyperbaric oxygen therapy is reported. Lack of reactivity to oxygenation is
partially dependent on the blood sugar concentration at the time and restoration of blood
sugar level to normal values will improve retinal reactivity. All patients with
proliferative or pre-proliferative diabetic changes should have their blood sugar levels
normalised at the time of treatment and any hypertension should also be controlled.
[EYE (1994) 8; 705-706]
Macular heterotropia
Macular heterotropia may be caused by congenital or acquired conditions (e.g.
persistent hyperplastic primary vitreous, Goldenhar syndrome, ROP, familial exudative
vitreoretinopathy coat
¢s
disease, trauma, Toxocara infection and also proliferative diabetic retinopathy). The
significant pathological findings in macular heterotropia associated with proliferative
diabetic retinopathy include dense fibrovascular tissue on the optic disc that correspond
to the nasal traction of the macula, a superior-nasally displaced fovea and an area of
stripped and recoiled internal limiting membrane overlying a retinal fold. Retinal pigment
epithelium reduplication may also be noticed and correspond to the clinically noticed
hyper-pigmented area superior to the heterotropic fovea. In spite of these changes the
visual acuity is often in the range of 20/40.
[Archives of Ophthalmology November 1994; 112: 1455-1459]
Simple retinal wrinkling associated with proliferative diabetic retinopathy causes mild
or no effects on the visual acuity, however significant macular heterotropia is associated
with more severe visual impairment. The visual prognosis and complications in patient who
had vitrectomy for macular heterotropia is compared with patient who had macular retinal
detachment duo to macular heterotropia to determine the role and indications of vitrectomy
in diabetic macular heterotropia. There is no significant difference between the two
groups in terms of visual acuity improvement, however a final postoperative visual acuity
better than 20/200 may be achieved in the treatment group and in only 48% of the patient
with macular detachment, whereas 47 % of the first group and only 10% of the second group
have better than 20/40 visual acuity. 10% of patient with macular detachment develop
neovascular glaucoma and 13% develop retinal detachment, but none of the patient treated
for macular heterotropia have this complication. These finding suggest that diabetic
macular heterotropia is a good indication for early vitrectomy
[Ophthalmology January 1994; 101: 63-67]
Diabetic papillopathy
Diabetic papillopathy is a syndrome of a relatively benign optic disc swelling that
occur mainly in young diabetics. The syndrome has been described almost exclusively in
patients with juvenile onset (type 1) diabetes typically presenting in the second or the
third decade of life. The clinical profile of this syndrome can now be expanded to include
older patients and also patients with type 2 diabetes. Affected eyes often have macular
oedema and retinal vascular changes that commonly affect the final visual outcome. Small
physiological cup may represent an anatomical predisposition to this condition. The
mechanism of diabetic papillopathy is speculative, it may be a representation of a
superficial retinal vascular disturbance or due to a deeper optic nerve vascular
compromise or axoplasmic flow disturbance.
[Archives of Ophthalmology July 1995; 113: 889-895]
Although the optic disc may appears normal, the Electrophysiologic function of the
optic nerve is occasionally abnormal in patients with diabetes but without retinopathy.
Retinal nerve fibre layer defects are common in patients with early diabetic retinopathy,
risk factors for the development of these defects are higher degrees of retinopathy,
systemic hypertension and advanced age.
[Ophthalmology August 1993; 100: 1147-1151]
Diabetic papillopathy may be associated with rapid progression of the diabetic
retinopathy and the development of disc neovascularisation. Patients with diabetic
papillopathy should be monitored closely for this risk.
[American Journal of Ophthalmology November 1995; 120: 673-675]
Florid diabetic retinopathy
Florid diabetic retinopathy is characterised by rapid progression of bilateral very
severe ischaemic retinopathy. It is often associated with a higher risk of vitreous
haemorrhage and blindness than with other forms of proliferative diabetic retinopathy.
Aggressive treatment with pan retinal laser photocoagulation and early vitrectomy (if
needed) may result in a much better outcome than with more conservative treatment. Most
patients with complications are of type 1 diabetes, which is often associated with other
systemic complications. Blindness can be prevented or delayed in up to 90% of patients by
using a rapid and full PRP and early vitrectomy if indicated.
[Ophthalmology April 1996; 103: 561-574]
Miscellaneous
This present study investigated the details of hyperopia changes in the
treatment of diabetes. 10 eyes of 5 diabetic patients showed bilateral transient hyperopia
between 1.1 and 4.9 dioptres after initiation of strict control of diabetes with or
without insulin. The hyperopia occurred within a few days and progressed to a maximum at
seven-fourteen days and then regressed gradually over a month. During hyperopia there was
no significant changes in axial lens or the corneal curvature, however thickened lens,
decreased anterior chamber depth and transient cataract were observed to a significant
degree. This transient hyperopia is most probably due to decreased lens refractive index
following water influx.
[British Journal of Ophthalmology March 1993; 77: 145-148]
K
This paper
report a case of solar retinopathy which was probably induced by a short period of diabetic
hypoglycaemia. Despite the fact that the patients was semiconscious during the time of
exposure the patients remembered gazing at the midday sun which resulted in this case in
bilateral central scotoma and bilateral solar retinopathy. Intensive insulin treatment and
subsequent hypoglycaemia can cause serious hazards to diabetic patients.
[Archives of Ophthalmology July 1994; 112: 982-983]
Medical treatment
Intensive diabetic treatment provide a substantial reduction in the risk of
developing clinically significant progression in diabetic retinopathy in all stages.
Glycaemic level as close to normal as considered safe should be aimed at.
[Archives of Ophthalmology January 1995; 113: 36-51]
Poor glycaemic control seems to be a cause of
clinically significant macular oedema. The risk of developing clinically significant
macular oedema, in patients with type 1 diabetes, increases with old age, male sex, poorer
blood glycaemic control.
[Ophthalmology August 1995; 102: 1170-1176]
Intensive treatment for diabetes aimed
at achieving a glycaemic levels as close to normal as possible does not completely prevent
diabetic retinopathy but it has a beneficial effect, that begins 3 years after treatment,
on all levels of diabetic retinopathy. It also reduces the need for laser photocoagulation
and the risk of visual loss. Intensive treatment for the diabetes should be the main
target as far as the patients visual outcome in concerned.
[Ophthalmology April 1995; 102: 647-661]
The relation between aggressive metabolic control and the diabetic retinopathy status
has not been well defined in patients with non-insulin dependent diabetes mellitus. It is
found that when treatment is changed from non-insulin to insulin to achieve a
better glycaemic control, diabetic retinopathy deteriorates over a period of 6 months.
This deterioration which is mainly in the form of cotton wool spots is much worse in older
people. Metabolic control in the elderly diabetic patients with established diabetic
retinopathy should be instituted more gradually.
[American Journal of Ophthalmology May 1993; 115: 569-574]
Progression of diabetic retinopathy is sometimes seen after the start of strict
glycaemic control probably due to changes in the retinal haemodynamics. Patient who
show progression in their diabetic retinopathy have typical retinal haemodynamics
characteristics. Measurement of the retinal blood flow after the institution of strict
diabetic retinopathy may help in identifying patient at greater risk of progression.
[British Journal of Ophthalmology August 1994; 78: 598-604]
The use of aspirin does nor seem to be associated with increase in vitreous or
pre-retinal haemorrhage in diabetic patient. Vitreous or pre-retinal haemorrhage in
diabetics should not be considered as a contraindication to aspirin.
[Archives of Ophthalmology January 1995; 113: 52-55]
In patients with diabetic retinopathy elevated serum lipid levels (total
cholesterol, low density lipoprotein cholesterol, and triglycerides) seems to be
associated with increased risk of having retinal hard exudate. Increasing amounts of hard
exudate seem to be independently associated with the risk of visual loss. Lowering serum
lipids may be associated with decreased risk of hard exudate development and visual loss.
[Archives of Ophthalmology September 1996;114: 1079-1084]
Pentoxifylline is a methyl xanthine derivative that has been used in the
treatment of vascular insufficiency diseases because of it
¢s ability to improve the blood flow. It has also been
shown that it can produce a vasodilatation effect in rats muscles. Oral administration of
Pentoxifylline in healthy volunteers produce a significant improvement in the retinal
capillary blood flow velocity and viscosity but not in filterability of the whole blood.
Pentoxifylline may be useful in the treatment of diabetic retinopathy.
[American Journal of Ophthalmology June 1993; 115: 775-780]
White blood cells are altered in diabetes and may cause vascular occlusions. Pentoxifylline
improves retinal capillary blood flow and whole blood viscosity in normal subjects and
also in diabetics. Pentoxifylline may have a role in the treatment of diabetic
retinopathy.
[Archives of Ophthalmology December 1993; 111: 1647-1652]
Pentoxifylline is used in peripheral vascular diseases because it has the
ability to increase the blood flow (due to its vasodilatation effect, decreasing the blood
viscosity and also due to its ability to improve the deformability of the red and white
blood cells). when used in healthy individual, Pentoxifylline causes an increase in the
pulsatile ocular blood flow in a dose dependent fashion supporting the possibility that
the drug might be useful in the treatment of several eye diseases e.g. diabetic
retinopathy.
[American Journal of Ophthalmology February 1996; 121: 169-176]
Surgical treatment (also see under vitreoretinal
surgery)
In eyes with diffuse diabetic macular oedema and no posterior vitreous detachment,
vitrectomy and induction of posterior vitreous detachment may be effective in resolving
the macular oedema with improvement of visual acuity for up to twelve months.
[American Journal of Ophthalmology August 1996;122: 258-260]
Diabetic vitrectomy for complications of severe proliferative diabetic retinopathy has
a valuable role in improving the patient overall visual function especially in patients
with vitreous haemorrhage.
[Ophthalmology November 1995; 102: 1688-1695]
Traction retinal detachment in diabetic patients can be treated by releasing the
anteroposterior traction on the retina by severing the posterior hyaloid attachments to
the fibrovascular membrane followed by segmentation or delamination of the membrane. A new
technique for "En-Block excision" of the posterior hyaloid and the fibrovascular
membrane is described. The results suggest that this technique allows similar visual
outcome, higher reattachment rates and less postoperative morbidity than previous reported
methods and a higher rates of iatrogenic retinal tears (which may be due to lack of
experience). 77% of eyes obtain 5/200 visual acuity or better and 97% of eyes remain
attached after 6-44 months of follow up.
[Ophthalmology May 1994; 101: 803-809]
Rubeosis is one of the most common postoperative complications in otherwise
successfully vitrectomised diabetic eyes especially in aphakic eyes even after silicone
oil tamponade. A significant correlation between worsening of iris diabetic
micro-angiopathy and both aphakia and severe postoperative inflammation exists. Eyes with
recurrent retinal detachments do not seem to have a significantly higher risk. On these
basis, complete retinal photocoagulation is warranted to prevent the iris
neovascularisation, the lens should be spared if possible and any postoperative
inflammation should be treated vigorously. Intraocular silicone does not appear to provide
protection in this study (unlike other studies).
[Ophthalmology August 1993; 100: 1152-1157]
Patients with type 1 diabetes with vitreous haemorrhage and proliferative diabetic
retinopathy can have an excellent visual prognosis after vitrectomy and endolaser retinal
photocoagulation when performed 1-6 months after the onset of the haemorrhage.
Preoperative scatter PRP may be helpful.
[Ophthalmology August 1995; 102: 1164-1169]
Diabetic patient with fibrovascular proliferation affecting the macular are (without
macular detachment) suffer from visual loss. About 11% to 22% of patient continue to show
signs of proliferation even after full laser pan-photocoagulation. Pars plana vitrectomy
in these cases may preserve useful vision in most of the patient. Surgeons do not need to
wait for retinal detachment before recommending surgical treatment.
[British Journal of ophthalmology June 1994; 78: 433-436]
Laser treatment
PRP may be followed by transient myopia that results from choroidal effusion. The
mechanism of this condition involves shallowing of the anterior chamber and forward
movements of the lens-iris diaphragm that results in myopia. Some patients seem to have
the tendency to develop this complication and may have bilateral changes. The anatomic
changes associated with this condition can be demonstrated by high frequency ultrasound
biomicroscopy.
[Archives of Ophthalmology October 1996;114: 1284-1285]
Focal treatment of diabetic macular oedema is often carried out by argon laser. It is
generally believed that focal laser treatment of diabetic macular oedema works mainly due
to laser absorption by the micro-aneurysms haemoglobin. Krypton and argon lasers seem to
be similarly effective in the treatment of diabetic macula oedema. Differential absorption
of the various laser wave lengths by haemoglobin in the micro-aneurysms may not be an
important factor in the success of laser treatment.
[British Journal of Ophthalmology April 1996; 80: 319-322]
Laser photocoagulation is useful in the treatment of diabetic clinically significant
macular oedema. The retinal and foveal thickness can be measured objectively by the
retinal thickness analyser using a green laser beam attached to a slit lamp biomicroscopy.
The level of foveal thickness before laser photocoagulation is strongly associated with
the level of thickness after the treatment. Laser treatment of a 60% increase macular
thickness has about 50% probability of reversal after treatment in 4 months while
treatment of a 180% increase thickness has only 2.5% probability of reversal within the
same period. Quantitative retinal thickness measurement provide an objective method of
assessing and monitoring laser treatment in diabetic patients with macula oedema.
[British Journal of Ophthalmology November 1994; 78: 827-830]
After focal laser photocoagulation for diabetic macular oedema a fibrous sub-pigment
epithelium membrane is noticed in some patients. These membranes may contribute to the
progressive enlargement of the laser scars.
[Archives of Ophthalmology May 1993; 111: 608-613]
There are a significant number of patients who experience intolerable pain during laser
pan retinal photocoagulation. If only one quadrant of PRP is needed sub-conjunctival
anaesthesia may be appropriate. If a full PRP is needed, no needle one quadrant sub-Tenon
anaesthesia can provide adequate anaesthesia without the need for sharp needle as in the
retrobulbar or the peribulbar methods. A small incision is made in the inferior temporal
bulbar conjunctiva by a Westcott scissors. A small amount of local anaesthetic is then
injected under the conjunctiva by a blunt curved cannula to raise a small bleb of the
conjunctiva and to help identify the Tenon layer. Another opening is made in the Tenon
capsule and the blunt tipped curved cannula in then introduced deep to the Tenon capsule
on the scleral surface where about 2 ml of lignocaine or 0.5% bupivacaine is injected.
[Eye(1993) 7; 768-771]
The main theoretical advantage of krypton red over argon blue-green laser in diabetic
retinopathy is the better penetration of the red light through red blood or yellow lens
nuclear sclerosis. Scatter laser photocoagulation with either the krypton red or argon
laser appears to be equally effective in the treatment of proliferative diabetic
retinopathy.
[Ophthalmology November 1993; 100: 1655-1664]
Laser photocoagulation is a proven method for treating diabetic macular oedema, it is
not exactly known how it works. After macular laser photocoagulation the macular
arterioles constrict 20% and the venules constrict 14%, this auto-regulatory
vasoconstriction result from the improved retinal oxygenation caused by the laser
treatment. Starling law predicts that vasoconstriction and reduced intravascular
hydrostatic pressure should reduce oedema formation in any tissue including the retina,
previous studies also showed reduced capillary diameter in animals retina after macular
grid laser photocoagulation.
[American Journal Ophthalmology January 1993; 115: 64-67]
Diabetic patients with proliferative diabetic retinopathy should be treated
aggressively with pan-retinal photocoagulation or cryotherapy or both. Regression of the
proliferative diabetic retinopathy is known to occur in about 93% of all treated patients.
More aggressive treatment (about 6500 of 500 micron burns) is needed in patients with high
risk factors (e.g. new vessels on the disc, severe new vessels, or pre-retinal or vitreous
haemorrhage), or in patients with longer duration of diabetes (more than 15 years) or in
patients younger than 30 years of age.
[American Journal of Ophthalmology June 1995; 119: 760-766]
Diode laser (810 nm) has the advantage of being compact, portable, easy to connect the
main electrical supply and easier to cool than Argon laser. By comparison with Argon
laser, Diode laser photocoagulation is confined to the retinal pigment epithelium and the
choroid and involves the sensory retina to a lesser degree, it might also be more painful
than the Argon laser. There is no difference in the clinical or visual response between
the two methods, however with the diode laser there is less decline in colour vision
sensitivity and pattern ERG than with the Argon laser. It is concluded that diode laser
photocoagulation may be a valuable alternative to Argon laser and it may be a more gentle
method of treatment.
[American Journal, Ophthalmology May 1994,117: 583-588]
Recently the continuos wave YAG laser in free running mode has been introduced for the
treatment of retinal and choroidal disorders. YAG laser does not seem as effective as
argon laser photocoagulation in the treatment of proliferative diabetic retinopathy.
[British Journal Ophthalmology July 1995; 79: 642-645]
It has been shown that diode laser can effectively be used to close leaking retinal
micro-aneurysms in patients with diabetic macular oedema. Diode laser has several
advantages over other laser systems (e.g. absence of laser energy absorption in the macula
and better transmission through lens opacities).
[British Journal of Ophthalmology April 1995; 79: 318-321]
Disruption of the blood-retinal barrier integrity has been implicated in the
pathogenesis of various proliferative vitreoretinal disease including diabetic retinopathy
and proliferative vitreoretinopathy. Previous studies demonstrated that the break down of
the blood-retinal barriers occurs during cryotherapy and laser photocoagulation. The new
near infra red semiconductor diode laser at wave length of 810 nm. Can be adaptable to
several delivery systems including a recently developed transscleral retinal contact
probe. this cryotherapy probe-like configuration of this instrument permits transscleral
contact photocoagulation with simultaneous monitoring and directing the treatment with the
indirect ophthalmoscopy. contact transscleral laser treatment is compared to cryotherapy
regarding the integrity of the blood-retinal barriers. transscleral contact laser
photocoagulation seems to induce less disruption of the blood-retinal barrier than the
conventional cryotherapy in rabbits eyes.
[Archives of Ophthalmology January 1995; 113: 96-102]
Pan-retinal photocoagulation is effective in the treatment of patients with
proliferative diabetic retinopathy. The mechanism of action is not completely understood.
It has been suggested that pan-retinal photocoagulation is associated with a local
increase in the retinal and the pre-retinal oxygen tension in the treated region which
causes vasoconstriction of the new vessels. Pan-retinal photocoagulation is also thought
to be associated by vascular narrowing which might lead to the regression of the new
vessels. Regional laser treatment produces regional reduction in the retinal blood flow
consistent with increases in the pre-retinal and retinal oxygen tension.
[British Journal of Ophthalmology May 1994; 78; 335-338]
Complications of pan retinal photocoagulation include damage to the iris, cornea or the
lens. Rise in the IOP may also occur with or without angle closure. Cilio-choroidal
effusion also occur in about 59% of patients after pan retinal photocoagulation treatment.
High resolution high frequency ultrasonography may be used to detect small degrees of
effusion. The cilio-choroidal effusion often resolve within 2 weeks. Effusion after pan
retinal photocoagulation seems to be associated with high intensity burns (which is
dependent on the laser setting and the amount of retinal pigmentation), the increased
number and size of laser burns and also with shorter axial length.
[Ophthalmology May 1996; 103: 827-832]
Breakdown of the blood-aqueous barriers can be measured by the laser flare- cell
photometer. Barrier break down occur after pan retinal photocoagulation particularly in
heavily pigmented eyes. Peak values occur after 24 hours an seem to subside after 72 to 96
hours. Clinically significant uveitis is uncommon. Neither successful nor unsuccessful pan
retinal photocoagulation treatment seem to be related to the degree of barriers break down
[Ophthalmology May 1996; 103: 833-838]
Pre-macular haemorrhage is common in patients with proliferative diabetic retinopathy.
Most of them occur in association with partial PVD. These haemorrhage are often slow to
clear and may result in rapid neovascular proliferation within the blood filled cavity
leading to epimacular membrane or macular traction retinal detachment. Early vitrectomy
has been recommended to avoid this complication, but may be associated with a high
incidence of operative and postoperative complications. YAG membranotomy has been used to
achieve rapid intravitreal drainage of the pre macular haemorrhage. YAG membranotomy may
obviate the need for early vitrectomy for dense pre macular haemorrhage and allows early
identification and treatment of any existing significant macular oedema before PRP thus
reducing the risk of exacerbation of the oedema after PRP. Complete intravitreal
dispersion of the blood can be achieved in most eyes within one week.
[Ophthalmology October 1996; 103:1568-1574]
Pre-macular haemorrhage could be associated with diabetes, valsalva haemorrhage or
retinal macro-aneurysm. A single or multiple applications of YAG laser membranotomy may be
beneficial in clearing the haemorrhage. Laser application allows the trapped blood to
enter the vitreous where it gets absorbed. This technique may be used in slowly clearing
or not clearing pre-macular haemorrhage associated with poor vision when vitreoretinal
surgery is not possible or not recommended.
[Ophthalmology March 1995; 102: 406-411]
Argon laser pan retinal photocoagulation may be associated with severe complication
e.g. visual field defects. Results show a 19% failure rate to reach driving standard after
laser treatment solely attributable to treatment which is at the lower end of previously
reported studies (20-80%). Modern treatment procedures for proliferative diabetic
retinopathy may be undertaken with the knowledge that in the majority of cases a patient
¢s driving licence is unlikely to be
revoked.
[EYE (1995) 9; 517-525]
Others
It is important to ensure that diabetic eyes are refracted and appropriate
magnifying glasses are provided as part of their treatment. In a study of 101 diabetic
patients, spectacle correction improved the vision for 29% of patients , half eye and
bifocal magnifiers improved vision for 30% of the patients, half eye in spectacle
magnifiers improved vision in 45% and hand held magnifiers improved vision for 11% of the
patients. Residual vision in diabetic retinopathy can be improved by optical treatment,
refraction and magnifiers.
[Ophthalmology January 1994; 101: 84-88]
Author
¢s note
Pregnant women with moderate to severe
retinopathy at conception are at greater risk of retinopathy progression. Patients who
have poor diabetic control at conception are also at higher risk. Women with diabetic
retinopathy should have their diabetes well controlled when they consider become pregnant.
Diabetes and
Glaucoma
It has been suggested that there is a statistically significant
association between diabetes and the incidence of primary open angle glaucoma. This study,
however found no evidence of this association.
[Ophthalmology January 1995; 102: 48-53]
The presence of primary open angle glaucoma is increased in people with older onset
diabetes. When considering the criteria of diagnosing primary open angle glaucoma the rate
in older onset diabetic is 4.2% versus 2% in non diabetic patients. When taking in
consideration patients who are taking treatment for glaucoma whether it is for the full
diagnostic criteria or not the rate is 7.8% in diabetes compared to 3.9% in non diabetics.
[Ophthalmology July 1994; 101: 1173-1177]
The effect of diabetes on visual function in patients with ocular hypertension is
significant. Colour vision, contrast sensitivity and pattern ERG are significantly reduced
in patients with diabetes and ocular hypertension relative to controls. Screening for
diabetes is recommended before drawing conclusions from the results of these tests in
patients with ocular hypertension. Race factors do not seem to play a major role in these
test results.
[Ophthalmology September 1996; 103: 1419-1425]
Diabetes and
the Cornea
It has been noticed that diabetic patients sustain a higher incidence of
corneal oedema after ocular surgery. Corneal endothelial function can be assessed by using
a single stress test. The test consists of pachymetry measurement of the corneal thickness
which is followed by a hydrophilic contact lenses wear to lower the oxygen
transmissibility to the cornea. Corneal swelling regression can then be quantified to
estimate the recovery rate per hour as an index of the corneal endothelial function.
Patients with non insulin dependent diabetes have a significant lower corneal endothelial
function and a higher potential for endothelial de-compensation after ocular surgery and
contact lenses wear. The corneal function capacity seems to decrease even further in
patients with diabetic retinopathy.
[Archives of Ophthalmology June 1996; 114: 649-653]
The corneal epithelium in diabetes is at high risk of damage during surgery or
photocoagulation. Animal studies indicate that the enzyme aldose reductase is involved in
this type of keratopathy. This randomised clinical study showed that topically applied
aldose reductase inhibitor (CT-112) is capable of reversing the corneal epithelial changes
and the reduced sensitivity in diabetic patients. It can also be effective in cases
unresponsive to other methods of treatment.
[American Journal of Ophthalmology March 1995;119: 288-294]
Polymegathism and pleomorphism are characteristic features of the corneal endothelium
in diabetic patients. Aldose reductase enzyme has been implicated in the pathogenesis of
some diabetic complications. Morphological variations of the endothelium of diabetic eyes
may resolve or improve within 3 months of treatment with topical application of aldose
reductase inhibitor (CT-112). Aldose reductase may be involved in the pathogenesis of
diabetic corneal endothelial changes.
[British Journal Ophthalmology December 1995; 79: 1074-1077]
In patient with insulin dependent diabetes mellitus, the corneal endothelial
permeability appears to be normal whereas the corneal auto-fluorescence, thickness
polymegathism and polymorphism are increased. in older patients with non insulin dependent
diabetes mellitus, the corneal changes are similar but do not differ significantly from
age matched controls. the effects of diabetes in these patients is probably masked by the
age changes. diabetes probably produce premature ageing of the cornea.
[Archives of Ophthalmology January 1996; 114: 9-14]
The cornea may be pathologically involved in diabetes. Increasing corneal thickness in
diabetics with retinopathy have been reported previously. The light scatter properties of
corneal oedema is a well known phenomena. No significant difference is found in the light
scattering properties of the central cornea between the diabetics and controls and this
technique does not seem to be useful in screening.
[EYE (1994); 8: 44-45]
#
The Ophthalmology Journal Review
Developed by Palmtrees Publishing as a
service to all ophthalmologists
Research by:-
Mr Magdy Nofal MBChB FRCS(Edinburgh) FRCOphth
Associate Specialist Ophthalmologist at Torquay.
The full review covers the following five leading journals :-
American Journal of Ophthalmology
Archives of Ophthalmology
British Journal of Ophthalmology
Eye
Ophthalmology
The period covers January 1993 to December 1996.
The scope includes all articles, reviews and even letters to the editor.
New versions cover dates up to the present and is available on CD-ROM.
Editorial Policy
Comment has been omitted because all material has
already been subject to peer review or editorial boards.
The Journal Review continues to be enlarged and enhanced.
We cannot take responsibility for any errors or omissions.
If in doubt go to the quoted source journal.
Contact
Published by Palmtrees Publishing
A subsidiary of Palmtrees Medical Informatics Ltd.
Microsoft
â
Solution Provider.
Creating solutions for health professionals.
Address:
Hesketh Road, Torquay, United Kingdom, TQ1 2LN.
Mobile phone:
UK 0370- 611-859 for your trial copy
Search Tip:
If you want to review articles about a subject in
a particular periodical use the search command NEAR.
For example to find references for :-
diabetes mellitus in Archives of Ophthalmology
search on "DIABETES NEAR ARCHIVES"
and set the search option -
"near means within 50 words".
You can configure options according to your needs.
Do use the search facility because this program contains
the equivalent of over four hundred pages of single
spaced A4 text. Let your computer take the strain.
Register to obtain the full version of the
"Ophthalmology Journal Review".
This is covers all aspects of Clinical Ophthalmology and will be
automatically released with the next Palmtrees CD-ROM.
We will give away the entire product for nothing! to registered
users of "Practical Ophthalmology" covering the period :
January 1993 to the end of December 1996. After that date we may
need to charge a small fee to cover the expense of continuous updates.
Further editions will be available either with "Practical Ophthalmology"
or separately via CD-ROM or our website :
www.infinite.co.uk/palmtrees
N.B. Authors of articles have been omitted in this version
but can be added in the future depending on demand.
