Evidence that upregulation of serum IGF-1 concentration can trigger acceleration of diabetic retinopathy

BACKGROUND—Acute reduction of chronic hyperglycaemia can accelerate early diabetic retinopathy. In adolescent patients with Mauriac's syndrome, this phenomenon is related to an upregulation of subnormal serum IGF-1 levels.
AIM—To obtain longitudinal data on serum IGF-1 and retinopathy status in poorly controlled adult insulin dependent (type 1) diabetic patients without Mauriac's syndrome, in whom hyperglycaemia is reduced by intensive insulin therapy.
METHODS—Four patients with chronic severe insulin deficiency and early microangiopathy were studied prospectively. Changes in plasma glucose, HbA_1c, serum IGF-1 levels, proteinuria, retinopathy, and clinical status were followed up closely.
RESULTS—Reducing hyperglycaemia from >16 mmol/l (equivalent to HbA_1c >11%) to <10 mmol/l (HbA_1c <8%) within 5 months increased serum IGF-1 levels by 70-220%. While proteinuria and symptomatic neuropathy regressed, retinopathy progressed from the mild to the severe non-proliferative stage with maculopathy (n=4), and to the proliferative stage (n=1). Laser coagulation was commenced upon the appearance of sight threatening macular oedema (n=4).
CONCLUSION—Upregulation of serum IGF-1 preceding retinal deterioration in these patients suggests a cause-effect relation, consistent with earlier experimental and clinical data.

Keywords: diabetes mellitus; macular oedema; metabolic control; intensive therapy; glycated haemoglobin A_1c; growth factors     

Retinal thickness variation in the diabetic patient measured by the retinal thickness analyser

AIM—To evaluate the potential of the retinal thickness analyser (RTA) as an objective tool for assessment and follow up of diabetic macular oedema.
METHODS—A prototype of the RTA that operates on the principle of laser slit biomicroscopy was used. Retinal thickness was obtained in 41 eyes of 41 diabetic patients. The clinical diagnosis was cystoid macular oedema (CMO) in 10 eyes, clinically significant macular oedema (CSMO) without retinal cysts in 21 eyes, and "dry" macula following grid pattern laser treatment in 10 eyes. The control group consisted of 46 eyes of age matched healthy volunteers.
RESULTS—In normal eyes (46 eyes), the foveal thickness measured was 178 (SD 44) µm and the macular thickness around the fovea was 311 (51) µm. The eyes with CMO displayed the largest foveal thickening, 875 (287) µm (390% increase compared with normal values). The average thickness of the fovea in the non-cystoid CSMO group was 427 (175) µm (144% increase compared with normal fovea). The average thickness of the foveal centre in eyes judged as having "dry" macula after laser treatment was 315 (71) µm (77% increase compared with normal value and a 26% decrease in thickness compared with the CSMO eyes). Statistically significant differences were found in central thickness between these four groups (p = 0.0001). The average thickness at 500 µm surrounding the fovea was 566 (202) µm in the CSMO eyes compared with 311 (51) µm in normal eyes (80% increase). The "dry" macula group (after undergoing laser treatments) had an average thickness of 414 (94) µm (27% decrease compared with CSMO eyes and a 33% increase compared with eyes of healthy controls).
CONCLUSIONS—RTA is a system for quantifying macular thickness and imaging of macular pathology. The system can be a useful tool for diagnosis of macular diseases and for evaluation of the effect of treatment modalities.

Keywords: diabetic retinopathy; retinal thickness; macular oedema; retinal imaging     

Scanning laser tomography Z profile signal width as an objective index of macular retinal thickening

AIMS—(i) To evaluate the relation between retinal thickness and the Z profile signal width of a scanning laser tomographer in selected patients exhibiting clinically manifest and circumscribed macular retinal thickening; (ii) to compare the Z profile signal width values of a group of age similar normal subjects with those of the patients with macular retinal thickening; and (iii) to present the methodology underlying the Z profile signal width derivation.
METHODS—Three patients with the following conditions were selected: widespread diabetic macular oedema; localised diabetic macular oedema; and macular hole. The patients were selected because they exhibited clinically manifest and circumscribed macular retinal thickening. Patients underwent fundus photography and a clinical examination which included fundus biomicroscopy. Fourteen age similar normal subjects were also assessed. The Heidelberg retina tomograph (HRT) was utilised to acquire seven topographic images of each macula. Z profile signal width data were analysed using custom software. Signal width was measured at 50% of the maximum intensity.
RESULTS—For each patient with macular retinal thickening, Z profile signal width analysis (after normalisation to reduce the influence of variation in reflectance intensity between successive images) revealed a significant (p<0.0001) localised increase of signal width which agreed with the HRT topographic analysis of retinal height, and also the clinical assessment of retinal thickness. The mean normalised Z profile signal width for the normal subjects (assessed over the whole image) ranged from 0.278 (SD 0.039) to 0.444 (0.063); these values compared with those obtained from patients in areas of macular retinal thickening of 0.761 (0.224) to 0.953 (0.194). Z profile signal width test-retest data for the patient with localised diabetic macular oedema were plus or minus 0.159 which compared with a mean signal width value of 0.761.
CONCLUSION—The evidence of this study, based upon three selected patients with macular retinal thickening and 14 normal subjects, would suggest that Z profile signal width analysis offers a non-invasive, objective, topographic, and reproducible index of macular retinal thickening. Studies employing larger sample sizes are required to determine the true clinical worth of the technique.

Keywords: diabetic macular oedema; retinal thickening; scanning laser tomography; Z profile     

A new colour vision arrangement test to detect functional changes in diabetic macular oedema

AIM—A study was undertaken to investigate the correlation between colour discrimination tests and the presence of macular oedema in patients with type I diabetes to find a sensitive diagnostic tool for the detection of early functional changes.
METHODS—The study was performed in 39 type I diabetic patients, 10 with and 29 without macular oedema. The examination included biomicroscopy, fundus photography of the macula, videofluorescein angiography, the LogMAR visual acuity chart, Farnsworth-Lanthony desaturated D-15 test, and the new Mollon-Reffin "Minimalist" test for colour vision deficiencies version 6.0.
RESULTS—A highly significant correlation was found between the tritan value of the Mollon test and the presence of clinically significant macular oedema (p<0.0015), with a high sensitivity (88.9%) and specificity (93.3%). The DD-15 test was not significant (p=0.345) and showed low sensitivity for the presence of macular oedema (36%). All variables concerning the grading of macular oedema showed a highly significant association with the tritan values of the Mollon test (p<0.0001).
CONCLUSION—The results suggest that the Mollon-Reffin "Minimalist" test version 6.0 is the best colour discrimination test for detecting macular oedema, with higher specificity and sensitivity than the other methods used in the study.

     

Altered retrobulbar vascular reactivity in early diabetic retinopathy

AIM/BACKGROUND—In diabetic eye disease the factors leading to compromised circulation and the resulting loss of visual function are poorly understood. Although retinal circulation has been widely investigated, it accounts for only a fraction of total eye blood flow. Blood flow was investigated in the larger vessels feeding the eye in patients with early diabetic retinopathy.
METHODS—Eleven patients with early diabetes with minimal or no retinopathy and 11 healthy controls were evaluated for retrobulbar blood flow velocity using colour Doppler imaging for the ophthalmic and central retinal arteries. Patients and subjects were tested while breathing room air and again under conditions of isocapnic hyperoxia.
RESULTS—Hyperoxia induced a significant change in the central retinal artery end diastolic velocity (EDV) (p = 0.008) and resistance index (RI) (p = 0.032) in normal subjects, but not in diabetic patients. Consequently, during hyperoxia, the diabetic patients were significantly higher for EDV (p = 0.006) and significantly lower for RI (p = 0.002) compared with normal controls. Hyperoxia caused no significant change in either group in the ophthalmic artery; nevertheless, under isocapnic hyperoxia conditions the diabetic patients had lower peak systolic velocity (p = 0.05) and lower RI (p = 0.05) than normal subjects.
CONCLUSIONS—Imposition of isocapnic hyperoxia produces significant differences in the ophthalmic and central retinal artery blood flow velocities in diabetic patients with early disease when compared with normal subjects. These results demonstrate that diabetic patients with minimal or no retinopathy suffer from irregular ocular vascular function in the major vessels feeding the eye.

     

Grid laser photocoagulation for macular oedema in uveitis or the Irvine-Gass syndrome

AIMS—To determine the effect of modified macular grid photocoagulation in patients with refractory macular oedema due to uveitis or cataract extraction.
METHODS—In this study 20 patients with macular oedema underwent modified macular grid laser photocoagulation and were followed by means of standardised examinations (day 0, months 2, 6, and 12) consisting of best corrected visual acuity and fluorescein angiography.
RESULTS—The mean visual acuity increased from 0.16 before to 0.3 after laser treatment (p=0.013), and fluorescein leakage was significantly reduced (p=0.005). Visual prognosis was influenced by duration of the uveitis, not by sex or age.
CONCLUSION—Modified macular grid laser photocoagulation had a beneficial effect on macular oedema caused by uveitis or the Irvine-Gass syndrome. A prospective, randomised study is needed to determine the exact place of modified macular grid photocoagulation in the treatment of patients with inflammatory or postsurgical macular oedema.

Keywords: macular grid photocoagulation; Irvine-Gass syndrome; macular oedema     

Qualitative and quantitative OCT response of diffuse diabetic macular oedema to macular laser photocoagulation

Purpose

To assess the quantitative and morphological changes of the macula in response to macular grid laser for diabetic macular oedema (DMO) using optical coherence tomography (OCT).

Patients and Methods

Cirrus OCT macular cube scans of 30 eyes of 25 patients were retrospectively analysed before and 4 months after macular grid laser for diffuse DMO. The oedema was quantified and response evaluated in the nine early-treatment diabetic retinopathy study (ETDRS) zones of the macula. Post-laser OCT changes were compared with the baseline features, including morphology patterns, changes in both logarithmic transformed (logOCT) and standardised average macular thickness (AMT), total macular volume, number of parafoveal quadrants involved, and the presence of intact 3rd hyper-reflective band (HRB).

Results

The rate of change of retinal thickness in response to laser was maximum in the central (8.17%) and perifoveal inferior quadrants (0.04%). Diffuse retinal thickening on OCT responded best to treatment. The AMT of 300–350 μm had the worst response (+0.94%). Eyes with less than four quadrants of oedema showed good response. Disrupted HRB was associated with poor visual gain (−0.33 ETDRS letters).

Conclusion

The topographic location of oedema on the retinal map and the morphological patterns of the oedema on OCT are useful predictors of treatment response in diffuse DMO.     

Sensitivity and specificity of a new scoring system for diabetic macular oedema detection using a confocal laser imaging system

AIM—To assess the use of the Heidelberg retina tomograph (HRT) in screening for sight threatening diabetic macular oedema in a hospital diabetic clinic, using a new subjective analysis system (SCORE).
METHODS—200 eyes of 100 consecutive diabetic patients attending a diabetologist's clinic were studied, all eyes had an acuity of 6/9 or better. All patients underwent clinical examination by an ophthalmologist. Using the HRT, one good scan was obtained for each eye centred on the fovea. A System for Classification and Ordering of Retinal Edema (SCORE) was developed using subjective assessment of the colour map and the reflectivity image. The interobserver agreement of using this method to detect macular oedema was assessed by two observers (ophthalmic trainees) who were familiarised with SCORE by studying standard pictures of eyes not in the study. All scans were graded from 0-6 and test positive cases were defined as having a SCORE value of 0-2. The sensitivity of SCORE was assessed by pooling the data with an additional 88 scans of 88 eyes in order to reduce the confidence interval of the index.
RESULTS—12 eyes in eight out of the 100 patients had macular oedema clinically. Three scans in three patients could not be analysed because of poor scan quality. In the additional group of scans 76 out of 88 eyes had macular oedema clinically. The scoring system had a specificity of 99% (95% CI 96-100) and sensitivity of 67% (95% CI 57-76). The predictive value of a negative test was 87% (95% CI 82-99), and that of a positive test was 95% (95% CI 86-99). The mean difference of the SCORE value between two observers was -0.2 (95% CI -0.5 to +0.07).
CONCLUSIONS—These data suggest that SCORE is potentially useful for detecting diabetic macular oedema in hospital diabetic patients.

     

Diabetic retinopathy in people aged 70 years or older. The Oulu Eye Study

AIMS—To evaluate the presence and severity of diabetic retinopathy and the value of retinopathy screening in people aged 70 years or older.
METHODS—In a population based study on 500 of 560 eligible (89%) people aged 70 years or older, signs of diabetic retinopathy were evaluated through dilated pupils by an ophthalmologist using photographic and/or ophthalmoscopic methods.
RESULTS—23% of the study population (113/500) had diabetes mellitus. Signs of diabetic retinopathy were found in 24 people (21% of the diabetic population). Retinopathy changes were graded as mild to moderate non-proliferative retinopathy (NPDR) in 40 eyes (18 people), severe NPDR (preproliferative) in five eyes (four people), and proliferative in three eyes (two people). Preproliferative or proliferative changes were present in four people (3.5% of the diabetic population) and diabetic maculopathy was diagnosed in nine (8% of the diabetic population). Laser treatment was considered to be indicated in seven people for maculopathy, and in two for proliferative changes. In four people the visual acuity was reduced to a low vision level as a result of diabetic retinopathy.
CONCLUSION—In spite of the high prevalence of diabetes mellitus in the elderly population, the prevalence of vision threatening diabetic retinopathy, particularly proliferative retinopathy, is low. Ophthalmoscopically, reliable information on fundus changes could be obtained in 94%, but photographs were gradable in only 76% of the diabetic population. Therefore, the value of photographic screening for diabetic retinopathy in this age group is poor in comparison with younger age groups.

     

Diabetic retinopathy in Down's syndrome

AIM—To determine the prevalence of diabetic retinopathy in patients with Down's syndrome and diabetes mellitus.
METHOD—Nine patients with Down's syndrome and diabetes mellitus were assessed. Factors recorded included type and duration of diabetes, level of diabetic control, blood pressure, urinalysis, and results of ophthalmological examination.
RESULTS—The duration of diabetes ranged from 8 to 41 years (mean 17.6 years). All had satisfactory glycaemic control and blood pressure measurements on the low side of normal (mean 106.6/70 mm Hg). One patient had early background diabetic retinopathy. The remainder had no evidence of diabetic retinopathy.
CONCLUSION—The low prevalence of diabetic retinopathy in these Down's syndrome patients, despite the long duration, is an interesting finding. It suggests some inherent protective factor against the development of diabetic retinopathy in this patient subgroup.

Keywords: Down's syndrome; retinopathy; diabetes; hypertension     

Partial reversal of protan and tritan colour defects with inhaled oxygen in insulin dependent diabetic subjects

AIMS—Abnormalities in colour perception occur early in the development of diabetic retinopathy. Whether these changes can be influenced by increasing circulating oxygen saturation was studied in comparison with non-diabetic controls.
METHODS—Protan and tritan colour thresholds were measured using a computer graphics system in 37 insulin dependent diabetic subjects, with no or minimal background retinopathy, and 27 matched controls. Colour thresholds were performed after subjects inhaled either gaseous air or 100% oxygen for a minimum of 5 minutes.
RESULTS—Diabetic subjects had higher colour vision thresholds when inhaling air when compared with controls (protan (mean 3.93 (SEM 0.39), v 2.36 (0.16), p<0.0002) and tritan (8.15 (0.62) v 5.42 (0.31), p <0.002)). The colour vision thresholds observed in diabetic subjects inhaling air fell when they inhaled oxygen (protan (3.93 (0.39) v 3.57 (0.33), p <0.025) and tritan (8.15 (0.62) v 7.35 (0.59), p<0.005)). No fall in colour thresholds was seen in non-diabetic controls who inhaled oxygen.
CONCLUSION—A small improvement in the colour vision thresholds was observed using computer graphics in diabetic subjects, with minimal or no retinopathy, who inhaled oxygen. This study supports a hypothesis that reduced retinal oxygenation contributes to the colour vision defects in diabetes.

     

Advanced glycation end products in human optic nerve head

AIMS—To localise advanced glycation end products (AGEs) in human optic nerve head.
METHODS—Optic nerve samples from 13 elderly individuals (seven diabetics and six non-diabetics) were obtained at necropsy. Pyrraline, an advanced glycation end product, was immunohistochemically localised in the optic nerve heads.
RESULTS—In the diabetic subjects, moderate to intense immunoreactivity for pyrraline was detected in sclera, pia mater, cribriform plates, connective tissues in the optic nerve, and around vessels in the optic nerve and pia mater. Immunoreactivity for pyrraline was also detected around retinal vessels. In the non-diabetic subjects, slight or no immunoreactivity for pyrraline was found in cribriform plates and around the optic nerve vessels.
CONCLUSION—Accumulation of AGEs in cribriform plates and around vessels in the optic nerve may contribute to the development of optic neuropathy in diabetic patients.

     

Longer term visual outcome of eyes with retinopathy of prematurity treated with cryotherapy or diode laser

AIMS—Visual outcome of 66 eyes in 37 patients who had undergone treatment with either cryotherapy or diode laser for threshold retinopathy of prematurity was assessed.
METHODS—17 patients, representing 30 eyes treated with cryotherapy, were examined at between 56 and 98 months corrected age (median 68 months). 20 patients representing 36 eyes treated with diode laser, were examined at between 30 and 66 months corrected age (median 51 months). Structural outcome was categorised as: optimal—flat posterior pole; suboptimal—macular ectopia, optic nerve hypoplasia, retinal fold involving the macula, and retinal detachment involving the macula.
RESULTS—Optimal structural outcome was, in the absence of amblyopia, associated with optimal visual acuity (of 6/12 or better) in all cases, with most eyes achieving a visual acuity of 6/9 or 6/6. Suboptimal structural outcome was invariably associated with suboptimal visual acuity. Amblyopia was present in eight out of 20 cryotherapy treated eyes and in five out of 26 laser treated eyes with an optimal structural outcome. Refractive errors were significantly less in laser treated eyes as was the incidence of anisometropic amblyopia.
CONCLUSION—Eyes treated with either cryotherapy or diode laser for threshold retinopathy of prematurity with optimal structural outcome are associated with development of optimal visual acuity—that is, 6/12 or better. Treatment with either cryotherapy or laser does not in itself reduce the visual potential of these eyes.

Keywords: retinopathy of prematurity; cryotherapy; laser; visual acuity     

The nanophthalmic macula

AIMS—To define an unusual macular appearance found in association with nanophthalmos.
METHODS—A case review.
RESULTS—Seven children (aged 8 months to 17 years) with nanophthalmos were examined. They all exhibited the same clinical findings of an unusual yellow macula appearance with retinal folds and crowded optic discs. Visual electrophysiology performed in four cases was normal.
CONCLUSION—A distinctive yellow macular pigmentation with associated chorioretinal folds and crowded optic discs is present in nanophthalmos. It is proposed that the retinal folds are due to a disparity between scleral and retinal growth while the macula discoloration is due to a congenital abnormality in arrangement or position of the luteal pigment and is not degenerative. Included in this case series is the second case in the literature of nanophthalmos associated with Kenny's syndrome. Inheritance of nanophthalmos appears to be autosomal recessive.

Keywords: nanophthalmos; maculopathy; Kenny's syndrome     

Plasminogen in proliferative vitreoretinal disorders

OBJECTIVE—Intravitreal fibrin formation is a frequent observation after vitrectomy performed for a variety of vitreoretinal disorders including proliferative vitreoretinopathy (PVR), proliferative diabetic retinopathy (PDR), and endophthalmitis. Plasminogen activators (PA) have been used for the management of this postoperative complication. This approach requires the presence of plasminogen, the substrate for PA mediated fibrinolysis, in the vitreal cavity.
METHODS—Quantification of plasminogen in the vitreous of 60 patients with PVR, PDR, and macular pucker was performed by streptokinase mediated activation using a chromogenic substrate. The presence of immunoreactive plasminogen was confirmed by immunoblot analysis of vitreal proteins and immunocytochemistry of surgically removed epiretinal membranes.
RESULTS—Plasminogen levels were dramatically increased in the vitreous of PVR and PDR patients compared with macular pucker patients and normal controls. Staining for plasminogen in epiretinal membranes was confined to the extracellular matrix. Predominant staining of perivascular areas in PDR specimens indicated that breakdown of the blood-retinal barrier is an important source of intravitreal plasminogen in that condition.
CONCLUSION—Plasminogen may play a role in traction membrane formation in PVR and PDR. Our biochemical analysis of presurgical vitreous indicates that there may be abundant substrate for PA mediated fibrinolysis in the vitreous cavity after vitrectomy.

     

Decreased choriocapillaris perfusion following surgical excision of choroidal neovascular membranes in age-related macular degeneration

AIMS/BACKGROUND—To evaluate macular changes following surgical excision of subfoveal choroidal neovascular membranes (CNVs) in age-related macular degeneration (AMD).
METHODS—The clinical records, fluorescein angiograms, and CNV histopathology of 12 patients with AMD who underwent surgical excision of subfoveal CNV were reviewed.
RESULTS—New areas of decreased choriocapillaris perfusion were noted by fluorescein angiography in the previous location of the CNV in 8/12 (75%) cases. Surgically excised tissue contained retinal pigment epithelium (RPE) in 11/11 specimens and choriocapillaris in 1/11 specimen studied.
CONCLUSIONS—Choriocapillaris atrophy may partly underlie the limited visual outcome following subfoveal surgery for AMD. Abnormal choriocapillaris perfusion following CNV excision may be due to pre-existing choriocapillaris atrophy, to choriocapillaris damage or removal at the time of surgery, or to RPE removal at surgery with abnormal RPE repopulation of the dissected area and subsequent choriocapillaris degeneration.

     

Fundus autofluorescence in patients with macular holes imaged with a laser scanning ophthalmoscope

AIM—To demonstrate the usefulness of a recently developed technique of imaging fundus autofluorescence and to compare it with the results of fluorescein angiography in the diagnosis and staging of macular holes.
METHODS—The intensity and distribution of fundus autofluorescence was studied in 51 patients with idiopathic macular holes and pseudoholes using a confocal laser scanning ophthalmoscope (cLSO) and the images were compared with those obtained by fundus fluorescein angiography.
RESULTS—Autofluorescence imaging demonstrated bright fluorescence of macular holes with appearance similar to that obtained by fluorescein angiography. In contrast macular pseuodoholes showed no such autofluorescence. The attached operculum in stage 2 macular holes and the preretinal operculum in stage 3 macular holes showed focal decreased autofluorescence. The associated retinal elevation and the cuff of subretinal fluid were less fluorescent compared with the background autofluorescence of the normal fellow eyes. Following successful surgical treatment the autofluorescence of the macular holes was no longer visible.
CONCLUSION—Autofluorescence imaging with the cLSO makes the assessment of macular holes possible with an accuracy comparable with that of fluorescein angiography. Being non-invasive and rapid, autofluorescence imaging may become a useful alternative to fluorescein angiography in the assessment and the differential diagnosis of full thickness macular holes.

Keywords: fundus autofluorescence; macular hole; lipofuscin; retinal pigment epithelium; laser scanning ophthalmoscope     

Prevalence and risk factors for diabetic retinopathy among Omani diabetics

AIMS—To study the prevalence of diabetic retinopathy in a population of patients attending a diabetic clinic and to evaluate the medical risk factors underlying its development.
METHODS—500 randomly selected diabetic patients attending the diabetes clinic in Al Buraimi hospital were referred to the ophthalmology department where they were fully evaluated for the absence or presence of retinopathy. Any retinopathy present was graded as mild non-proliferative retinopathy (NPR), moderate-severe NPR, and proliferative retinopathy. Several risk factors were then evaluated in order to delineate those related to occurrence of retinopathy in general as well as to the different grades of retinopathy in particular.
RESULTS—Diabetic retinopathy was detected in 212 patients (42.4%), with mild NPR present in 128 patient (25.6% of the total population), moderate-severe NPR in 20 patients (4%), and proliferative diabetic retinopathy present in 64 patients (12.8%). Factors significantly related to occurrence of retinopathy were age of the patient, duration of diabetes, presence of ischaemic heart disease, presence of hypertension, a high fasting capillary glucose level as well as elevated serum levels of urea, creatinine, cholesterol, and triglycerides. After adjustment for covariates, it was found that duration of diabetes was the only risk factor associated with mild NPR, while high diastolic blood pressure and high levels of serum creatinine, cholesterol, and triglycerides were significantly associated with the occurrence of proliferative retinopathy.
CONCLUSIONS—In addition to glycaemic control, lowering of blood lipids as well as diastolic blood pressure (in hypertensive patients) may be effective in lowering the incidence of retinopathy in compromised patients.

Keywords: diabetic retinopathy; Oman; diabetics     

VEGF localisation in diabetic retinopathy

AIM—To determine the staining pattern of vascular endothelial growth factor (VEGF) at different stages of diabetic retinopathy (including post-laser photocoagulation) and to compare staining in excised fibrovascular and fibrocellular (non-diabetic) preretinal membranes.
METHODS—Immunohistochemical localisation of VEGF, using antibodies raised against VEGF₁₆₅ and VEGF_121,165,189, was carried out on specimens of normal human retina (n=15), diabetic retinas ((a) with no overt retinopathy (n=19), (b) with intraretinal vascular abnormalities but no proliferative retinopathy (n=6), (c) with active proliferative retinopathy (n=6), (d) with no residual proliferative retinopathy after photocoagulation therapy (n=15)), excised diabetic fibrovascular membranes (n=19), and non-diabetic fibrocellular membranes (n=7). The degree and pattern of immunostaining was recorded.
RESULTS—In general, VEGF was absent from the majority of normal retinas. VEGF staining was apparent in most diabetic tissues but the staining pattern was dependent on both the specificity of the antibody used and the category of tissue. Staining with the VEGF₁₆₅ antibody was generally confined to endothelial cells and perivascular regions while the VEGF_121,165,189 antibody was also associated with extravascular components of the inner retina. Intensity of immunostaining of diabetic eyes was dependent on the severity of retinopathy being least in diabetics with no overt retinopathy and greatest in retinas with proliferative retinopathy. Interestingly, the intensity of immunostaining in diabetic retinas which had undergone laser surgery for proliferative retinopathy was reduced to basal levels. Moderate to intense immunostaining was observed in all fibrovascular and fibrocellular membranes examined.
CONCLUSIONS—This study supports a circumstantial role for VEGF in the pathogenesis of both the preclinical and proliferative stages of diabetic retinopathy.

Keywords: vascular endothelial growth factor; VEGF; diabetes; diabetic retinopathy     

Complicated posterior capsulorhexis: aetiology, management, and outcome

BACKGROUND—A 1 year retrospective analysis of 650 patients, who underwent a posterior capsulorhexis on their intact capsules, was performed to examine the incidence of complications, their aetiologies, and the outcome.
METHODS—Data were analysed on 32 patients with complicated capsulorhexis for type of surgery, preoperative and postoperative factors, and relative risk factors for vitreous issue.
RESULTS—There were six patients with vitreous loss. The posterior capsulorhexis was uncontrolled in 14 cases and difficult to perform in 12 cases. Implantation into the capsular bag was possible in all cases. Systemic vascular hazard and old age (over 80 years) were found to be statistically significant risk factors for vitreous loss (p=0.002 and p=0.03 respectively). The mean follow up was 13.5 months (range 4-25 months). One patient developed a retinal detachment and two had a transient clinical cystoid macular oedema. Visual acuity of ≥ 20/40 was obtained in 93% of the patients.
CONCLUSION—Loss of control of the posterior capsulorhexis has a low incidence but can lead to serious problems during surgery. A good knowledge of the technique is necessary to complete the procedure with a posterior capsulorhexis of the optimum size without vitreous loss.