Retinal vessel dilatation and elongation precedes diabetic macular oedema

AIMS/BACKGROUND—Retinal vessel dilatation is a well known phenomenon in diabetes. In this study, the theory of whether excessive changes in diameter and length of retinal vessels occur in the development of diabetic macular oedema was tested, supporting a hypothesis that the development of diabetic macular oedema may be linked to hydrostatic pressure changes described in Starling's law.
METHODS—From fundus photographs of diabetic patients attending a regular eye screening programme, the diameter and segment length of retinal vessels were measured in three retinopathy groups (12 patients each) with diabetic macular oedema (DMO), background retinopathy and no retinopathy, over a period of approximately 4 years, ending at the time of diagnosis of diabetic macular oedema in the DMO group.
RESULTS—A statistically significant dilatation and elongation of retinal arterioles, venules, and their macular branches was found before the diagnosis of macular oedema in the DMO group. No significant changes were found in the other two groups.
CONCLUSION—It is suggested that Starling's law applies to the formation of oedema in the retina as in other tissues.

     

Prevalence of diabetic retinopathy in patients with diabetes mellitus diagnosed after the age of 70 years

AIMS/BACKGROUND—A hospital based prevalence study was undertaken to estimate the prevalence of diabetic retinopathy (DR) in patients diagnosed as having diabetes mellitus after the age of 70 years. The prevalence of visually threatening retinopathy at the time of diagnosis of diabetes was also determined. The association between prevalence of DR and duration of diabetes mellitus, mode of treatment, HbA_1c levels, presence of hypertension, and sex of patient was examined and a comparison was drawn between this study and earlier prevalence studies of DR in older type II diabetics.
METHODS—Using data on the Irish Diabetic Retinopathy Register located in the Mater Misericordiae Hospital, Dublin, all patients who were diagnosed as having type II diabetes mellitus after the age of 70 years were invited to attend for ophthalmic review. Medical records were examined to determine the duration of diabetes mellitus, mode of treatment, recent HbA_1c levels, and the presence of systemic hypertension.
RESULTS—Of the 150 patients examined, 21 (14%) had some form of DR and 10 of these patients (6.6%) had visually threatening retinopathy or previously treated visually threatening retinopathy. Five patients (3.3%) presented with visually threatening retinopathy at the time of diagnosis of diabetes. Those patients with DR had a significantly higher median duration of diabetes (5.0 years) compared with those patients without DR (3.5 years). A significantly higher proportion of patients with DR required treatment with insulin and a correspondingly lower proportion of patients without DR were controlled on diet alone. There was no significant association between prevalence of DR and HbA_1c levels, systemic hypertension, or sex of patient. There was a lower overall prevalence of DR in comparison with earlier studies.
CONCLUSIONS—The prevalence of DR in these elderly type II diabetics is lower than that previously reported in patients with type II disease but a small percentage of patients had visually threatening retinopathy at presentation. Longer duration of diabetes and insulin use were associated with a significantly increased prevalence of DR. All elderly type II diabetic patients require thorough ophthalmic examination near to the time of first presentation and thereafter at regular intervals.

     

Serum total renin, an independent marker of the activity and severity of retinopathy in patients with IDDM

BACKGROUND/AIMS—Recent studies have demonstrated marked renin and prorenin concentration gradients between ocular tissues and blood, and local expression of the renin-angiotensin system (RAS) in the eye. The authors determined whether serum total renin, which mostly consists of prorenin, is a marker of the activity and severity of diabetic retinopathy independent of other microvascular complications.
METHODS—Total renin concentrations (TRC) were measured with a time resolved immunofluorometric assay in 38 patients with IDDM (age 34 (SD 7) years, duration of disease 22 (7) years, serum creatinine 95 (15) µmol/l, urinary albumin excretion rate (UAER) 207 (829) µg/min, HbA_1c 8.5% (1.2%)), and in 13 matched normal subjects. All subjects were carefully characterised with respect to the presence and severity of retinopathy (RP score), nephropathy, and neuropathy using seven different tests of autonomic neuropathy.
RESULTS—Serum TRC was on average twofold higher in IDDM (396 (SE 211) ng/l) than in normal subjects (201 (88) ng/l, p<0.001). It was nearly twofold higher in patients with preproliferative or active proliferative retinopathy requiring careful follow up or therapy (TRC 596 (268) ng/l, n=11) compared with those with quiescent proliferative retinopathy after laser treatment (TRC 338 (183) ng/l, p<0.01, n=5); moderately severe non-proliferative retinopathy (337 (106) ng/l, p<0.01, n=13), no retinopathy, or only minimal non-proliferative retinopathy (270 (43) ng/l, p<0.001, n=9). In multiple linear regression analysis, RP score (p<0.01), but not the UAER or any index of autonomic neuropathy, was an independent determinant of serum TRC, and explained 32% of its variation (R=0.57, p<0.005).
CONCLUSIONS—Serum TRC in patients with diabetic retinopathy is increased independent of renal function and autonomic neuropathy, especially in those with severe active changes requiring careful follow up or treatment. These findings support the idea that diabetic retinopathy is the most important determinant of serum TRC in patients with IDDM, and that TRC is produced when retinopathy is active.

Keywords: diabetes; prorenin/total renin; retinopathy; nephropathy; neuropathy     

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     

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.

     

Elevated serum IL-8 levels are associated with disease activity in idiopathic intermediate uveitis

AIM—To find a laboratory indicator for systemic involvement in intermediate uveitis.
METHODS—Interleukin 8 (IL-8) and C reactive protein (CRP) serum levels were measured in patients with idiopathic intermediate uveitis (n=61), uveitis controls (n=143), and normal controls (n=29). The records of those with intermediate uveitis were reviewed with the emphasis on disease activity and severity as characterised by the presence of cystoid macular oedema, vitreous exudates or snowbank formation, papillitis, and periphlebitis.
RESULTS—Increased serum IL-8 (20 pg/ml) was found in 27 out of 61 patients with intermediate uveitis (p< 0.01), 12 of 27 patients with sarcoid uveitis (p<0.05), in 19 of 30 patients with HLA-B27 associated acute anterior uveitis (p<0.05), and in five of 29 healthy controls. Raised IL-8 levels in intermediate uveitis were significantly associated with active disease (p<0.001) and the presence of vitreous exudates (p<0.001), papillitis, and periphlebitis (p<0.01). Elevated CRP levels were found in 12 of the 143 uveitis controls but in none of the intermediate uveitis patients or normal controls. During follow up an associated systemic disease was more frequently noticed in patients with an elevated serum IL-8 at entry into the study.
CONCLUSIONS—Elevated IL-8 serum levels were found in patients with active intermediate uveitis of unknown origin. An elevated IL-8 level seems to predispose the patient to a later development of associated systemic disease.

Keywords: C reactive protein; interleukin 8; uveitis; multiple sclerosis; sarcoidosis     

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     

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.

     

Treatment of ocular symptoms of Behçet's disease with interferon α2a: a pilot study

AIM—To study long term effects of interferon α_2a (IFNα_2a) on panuveitis in seven patients with Behçet's disease in a prospective, open clinical trial.
METHODS—Seven patients were treated with IFNα_2a for a mean of 23.6 months (14-37 months). They received an initial dose of IFNα_2a of 6×10⁶ IU/day, followed by 3×10⁶ IU/day after 1 month and 3×10⁶ IU every other day after 3 months. Two patients received low dose prednisolone (between 0.2 and 0.4 mg/kg/body weight) additionally at the beginning of the therapy. Complete cessation of IFNα_2a was possible in three patients (observation period 22, 6, and 4 months).
RESULTS—Marked improvement occurred in six patients who had ocular manifestations of Behçet's disease for the first time or with minor damage during their course of chronic relapsing panuveitis. In one patient with advanced ocular Behçet's disease, new relapses were prevented. Retinal infiltrates resolved within 2 weeks; vasculitis, macular oedema, infiltration of the anterior chamber and vitreous resolved within 4 weeks. Mean posterior uveitis score before treatment (nine affected eyes) was 6.6, 4 weeks after IFN it was reduced to 0.4. The mean observation period is 27.6 months, ranging from 14 to 42 months.
CONCLUSION—Treatment of ocular symptoms of Behçet's disease with IFNα_2a alone or in combination with low dose steroids led to complete remission of ocular vasculitis in all patients treated in this open, uncontrolled trial. Treatment with IFNα_2a may prevent permanent retinal or optic nerve damage due to vascular occlusion. No severe side effects occurred. Controlled randomised studies are warranted in order to prove the efficacy of IFNα_2a in ocular Behçet's disease and to compare it with other, established treatments such as azathioprine or cyclosporin A.

Keywords: Behçet's disease; uveitis; interferon α_2a     

Surgical management of macular holes: results using gas tamponade alone, or in combination with autologous platelet concentrate, or transforming growth factor β2

BACKGROUND—Vitrectomy and gas tamponade has become a recognised technique for the treatment of macular holes. In an attempt to improve the anatomic and visual success of the procedure, various adjunctive therapies—cytokines, serum, and platelets—have been employed. A consecutive series of 85 eyes which underwent macular hole surgery using gas tamponade alone, or gas tamponade with either the cytokine transforming growth factor β2 (TGF-β2) or autologous platelet concentrate is reported.
METHODS—Twenty eyes had vitrectomy and 20% SF₆ gas tamponade; 15 had vitrectomy, 20% SF₆ gas, and TGF-β2; 50 had vitrectomy, 16% C₃F₈ gas tamponade, and 0.1 ml of autologous platelet concentrate prepared during the procedure.
RESULTS—Anatomic success occurred in 86% of eyes, with 96% of the platelet treated group achieving closure of the macular hole. Visual acuity improved by two lines or more in 65% of the SF₆ only group, 33% of those treated with TGF-β2, and in 74% of the platelet treated group. In the platelet treated group 40% achieved 6/12 or better and 62% achieved 6/18 or better. The best visual results were obtained in stage 2 holes.
CONCLUSION—Vitrectomy for macular holes is often of benefit and patients may recover good visual acuity, especially early in the disease process. The procedure has a number of serious complications, and the postoperative posturing requirement is difficult. Patients need to be informed of such concerns before surgery.

     

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.

     

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.

     

Increased presence of Epstein-Barr virus DNA in ocular fluid samples from HIV negative immunocompromised patients with uveitis

AIMS—To investigate whether routine testing for Epstein-Barr virus (EBV) is necessary in the examination of a patient with uveitis.
METHODS—Intraocular EBV DNA was determined in 183 ocular fluid samples taken from patients with AIDS and uveitis, HIV negative immunocompromised uveitis, acute retinal necrosis, toxoplasma chorioretinitis, intraocular lymphoma, anterior uveitis, and miscellaneous uveitis of unknown cause. In 82 samples from this group of patients paired serum/ocular fluid analysis was performed to detect local antibody production against EBV. Controls (n=46) included ocular fluid samples taken during surgery for diabetic retinopathy, macular pucker, or cataract.
RESULTS—Serum antibody titres to EBV capsid antigen proved to be significantly increased in HIV negative immunocompromised patients with uveitis (p<0.01) compared with controls. Local antibody production revealed only three positive cases out of 82 patients tested, two results were borderline positive and one patient had uveitis caused by VZV. EBV DNA was detected in three out of 46 control ocular fluid samples. In the different uveitis groups EBV DNA was noted, but was not significantly higher than in the controls, except in six out of 11 HIV negative immunocompromised patients (p=0.0008). In four out of these six cases another infectious agent (VZV, HSV, CMV, or Toxoplasma gondii) had previously been identified as the cause of the uveitis.
CONCLUSIONS—When comparing various groups of uveitis patients, EBV DNA was found more often in HIV negative immunocompromised patients with uveitis. Testing for EBV does not have to be included in the routine management of patients with uveitis, since indications for an important role of this virus were not found in the pathogenesis of intraocular inflammation.

Keywords: Epstein-Barr virus; intraocular fluid; polymerase chain reaction; uveitis     

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     

Systemic and local immunological features of atopic dermatitis patients with ocular complications

AIMS—Clinical factors and data from recent cases of atopic dermatitis (AD) (with or without ocular complications) and non-AD cases were examined to evaluate the mechanism of atopic ocular complications.
METHODS—IgE-RAST for eight allergens including rice, egg, and mite and serum total IgE were measured in 216 patients with AD (70 ocular type, 146 non-ocular type) and 69 non-AD individuals. Tear histamine and leukotriene B₄ (LTB₄) levels were also measured.
RESULTS—The serum levels of IgE were significantly increased in AD patients with ocular complications compared with those without ocular complications. The positive rates of IgE-RAST for rice and wheat were significantly higher in ocular type AD than in non-ocular type AD. In ocular type AD, serum IgE was significantly increased in patients with cataract compared with that in those without cataract. Tear histamine and LTB₄ levels in AD patients with ocular complications showed significant elevations compared with those in patients with pure AD and controls.
CONCLUSIONS—These results suggest that ocular type AD belongs to the most severe end of the spectrum of AD, and that some food antigens may contribute to the pathogenesis of severe AD resulting in ocular complications.

Keywords: atopic dermatitis; IgE-RAST; histamine; leukotriene B₄     

Vitreous intercellular adhesion molecule 1 in uveitis complicated by retinal detachment

AIMS—The vitreous levels of soluble intercellular adhesion molecule 1 (sICAM-1) were investigated in uveitic eyes undergoing vitrectomy for retinal detachment (RD) or other complications, and the presence of this molecule was related to disease activity and vitreous levels of the cytokine tumour necrosis factor α (TNFα), known to upregulate ICAM-1 expression on various cells.
METHODS—Vitreous and serum samples from 23 patients with either active or quiescent uveitis undergoing retinal surgery were examined for the levels of immunoreactive sICAM-1 and TNFα by ELISA methods, and for the presence of biologically active TNFα. Vitreous from non-uveitic eyes with rhegmatogenous retinal detachment (RRD), macular holes or cadaveric eyes were used as controls.
RESULTS—As a whole, vitreous from uveitic eyes complicated or uncomplicated by RRD contained significantly higher levels of sICAM-1 than vitreous from non-uveitic eyes with RRD alone (p < 0.0005), eyes with macular holes (p< 0.0001), or normal cadaveric vitreous (p < 0.0001). The proportion of vitreous containing >20 ng/ml sICAM-1 (> four times the normal values) was significantly higher in eyes with uveitis complicated by RRD than in those eyes without RRD (Fisher's test, p= 0.02), and although levels of sICAM-1 were higher in eyes with active uveitis than in those with quiet disease (p < 0.02), this could not be dissociated from the increase caused by RRD. There was a relation between the vitreous levels of sICAM-1 and those of immunoreactive TNFα (Spearman's correlation coefficient; r = 0.601, p = 0.006), but not between the vitreous levels of sICAM-1 and those of biologically active TNFα.
CONCLUSION—Increased vitreous sICAM-1 levels and the association of this molecule with the presence of immunoreactive TNFα in uveitic eyes confirm the operation of cytokine mediated vascular reactions at the blood-retinal barrier during the development of this condition. The persistence of high vitreous levels of sICAM-1 in eyes with uveitis complicated by RRD despite previous immunosuppression may indicate a low rate of clearance of inflammatory molecules from the vitreous cavity and an exacerbation of the existing inflammatory process by the retinal detachment itself.

Keywords: vitreous; retinal detachment; ICAM-1; TNFα; uveitis     

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     

Effect of isovolaemic haemodilution on visual outcome in branch retinal vein occlusion

AIMS—To assess the efficacy of isovolaemic haemodilution therapy (IHT) in the treatment of patients with branch retinal vein occlusion (BRVO).
METHODS—Patients presenting with BRVO between 1 July 1991 and 31 August 1993 were eligible for inclusion and randomised into treatment and control groups. Patients randomised to receive IHT were treated for 6 weeks with venesection and volume replacement using hydroxyethylstarch, a plasma expander. The target haematocrit was 35%. Follow up was for 1 year.
RESULTS—The baseline visual acuity of the two groups was similar at 0.74 and 0.75 logMAR units (Snellen 6/36), for the IHT and control groups, respectively. At 6 weeks, visual acuity in the IHT group had improved by 0.20 logMAR units (2 lines on the Bailey-Lovie chart) (p=0.0001). Vision was unchanged in the control group. At 1 year, the IHT group exhibited an improvement of 0.43 logMAR units. By comparison, the improvement in the control group at 1 year was significantly less at 0.17 logMAR units (p=0.03). The final visual acuity in the IHT and control groups was 0.30 (Snellen 6/12) and 0.60 (Snellen 6/24) logMAR units, respectively.
CONCLUSIONS—The results support the theory that IHT has a positive effect on the visual outcome in patients with BRVO.

Keywords: branch retinal vein occlusion; haemodilution; laser treatment; macular oedema