Glycaemic threshold for diabetes-specific retinopathy among individuals from Saudi Arabia, Algeria and Portugal.

We studied the glycaemic threshold and prevalence of diabetic retinopathy in screen-detected diabetes in Saudi Arabia, Algeria and Portugal. The prevalence of diabetes-specific retinopathy started to increase at an HbA1c level of 6-6.4% (42-47 mmol/mol) and in individuals with HbA(1c) >7.0% the prevalence was 6.0%.

Impact of changes in metabolic control on progression to photocoagulation for clinically significant macular oedema: a 20 year study of type 1 diabetes.

AIMS/HYPOTHESIS: Although increasing hyperglycaemia, arterial hypertension and longer duration of diabetes raise the risk of progression of diabetic retinopathy, short-term benefits in terms of improved metabolic control and lowered blood pressure have not been demonstrated. We therefore examined the effect of changes in glycaemia and arterial blood pressure on the incidence of clinically significant macular oedema in a population of diabetic patients. METHODS: We performed a retrospective review of all patients with type 1 diabetes who attended the retinopathy screening clinic at the Steno Diabetes Center from 1988 to 2008, using the endpoint referral to first photocoagulation treatment for clinically significant diabetic macular oedema. The analysis included 1,878 patients (median observation, 8 years). Changes were defined as the inter-visit change; in the case of an event the last event-free interval before referral, where the median screening interval was 6 months. RESULTS: Risk of progression to photocoagulation for macular oedema increased with duration of diabetes (p < 0.001), current HbA1c (p < 0.0001) and with the magnitude of changes in HbA1c (p = 0.0002) and systolic blood pressure (p < 0.0001) in a multiple regression model. A recent decrease of ≥ 0.5 percentage points or an increase in HbA1c of >0.5 percentage points per 6 months was associated with HRs of 3.04 and 1.28, respectively, compared with lesser changes in HbA1c. CONCLUSIONS/INTERPRETATION: In this study, large recent changes in metabolic control and systolic blood pressure, irrespective of direction, were independent risk factors for progression to photocoagulation for diabetic macular oedema. The effects of metabolic and haemodynamic stability on diabetic retinopathy should be examined in prospective studies.

Cumulative glycaemia as measured by lens fluorometry: association with retinopathy in type 2 diabetes.

AIMS/HYPOTHESIS: The aim of this study was to assess the association between lifelong cumulative glycaemia estimated by lens fluorometry and the presence of retinopathy in individuals with type 2 diabetes. METHODS: We carried out a cross-sectional population-based study of 970 participants aged between 30 and 60 years, of which 170 were diagnosed with diabetes on screening (WHO 1999 criteria) and 35 had known type 2 diabetes. Procedures included clinical and laboratory examinations, non-invasive assessment of the intrinsic fluorescence of the lens of the eye, and seven-field fundus photography. RESULTS: Retinopathy was found in 46 (22%) of 205 participants with type 2 diabetes. In a logistic regression analysis controlling for age, sex and diabetes status (screen-detected or known), a two-fold increase in lens fluorescence increased the odds for retinopathy by 3.46 (95% CI 1.25-9.55, p = 0.017). The association was marginally significant (OR 3.00 [95% CI 1.00-9.01], p = 0.050) when also adjusted for smoking, systolic blood pressure, body mass index and HbA(1c). CONCLUSIONS/INTERPRETATION: Diabetic retinopathy was related to cumulative lifelong glycaemia as estimated by lens fluorometry in participants with type 2 diabetes. This supports the hypothesis that retinopathy is a marker of lifelong elevated glycaemia as well as of the unknown, pre-diagnostic duration of type 2 diabetes. The powerful association between lens fluorescence and retinopathy underscores the importance of strict long-term glycaemic control in the prevention of retinopathy in people with diabetes.

Endothelial dysfunction and low-grade inflammation and the progression of retinopathy in Type 2 diabetes.

AIMS: To study whether microalbuminuria, endothelial dysfunction and low-grade inflammation are associated with the presence and progression of diabetic retinopathy. METHODS: Patients with Type 2 diabetes (n = 328) attending a diabetes clinic were followed for 10 years and examined annually during the last 7 years. Retinopathy was assessed after pupillary dilatation by direct ophthalmoscopy (baseline) and two-field 60 degrees fundus photography (follow-up). Urinary albumin excretion, and markers of endothelial function (von Willebrand factor, tissue-type plasminogen activator, soluble E-selectin (sE-selectin), and soluble vascular cell adhesion molecule 1) and inflammatory activity (C-reactive protein and fibrinogen) were determined. RESULTS: The prevalence of retinopathy was 33.8%. The median diabetes duration at baseline was 7 years (interquartile range 2-12 years). The highest tertiles of baseline urinary albumin excretion and glycated haemoglobin (HbA(1c)) were associated with prevalent retinopathy: odds ratio (OR) 95% confidence interval (CI) 2.80 (1.44-5.46) and 2.19 (1.11-4.32), respectively. Progression of retinopathy occurred in 188 patients. The second and third tertiles of baseline sE-selectin were associated with progression of retinopathy [1.44 (1.04-2.01) and 1.61 (1.19-2.18)] but not independently of HbA(1c). None of the other markers was significantly associated with the presence or progression of retinopathy. High baseline HbA(1c) was significantly associated with progression of retinopathy: 1.65 (1.21-2.25). CONCLUSIONS: In this population of patients with Type 2 diabetes who attended a diabetes clinic, there was some evidence for a role of endothelial dysfunction in the progression of retinopathy. We could not demonstrate a role for low-grade inflammation. Our study emphasizes the importance of glycaemic control in the development and progression of retinopathy.

Diabetic macular oedema: a clinical overview.

Diabetic retinopathy is the leading cause of blindness in working aged-adults in westernised countries. Diabetic macular oedema (DMO) is a manifestation of diabetic retinopathy and is the leading cause of the visual impairment that occurs with diabetic retinopathy. There are multiple ways of classifying DMO; however, none appear to be wholly satisfactory. DMO occurs more frequently in type 2 diabetes mellitus, and appears to be more prevalent as the duration of diabetes increases, and as the severity of diabetic retinopathy worsens. There are multiple risk factors in common with diabetic retinopathy, such as hyperglycaemia, hypertension and dyslipidaemia; however, specific factors such as the presence of renal disease appear to be more significantly associated with DMO. Whereas the gold standard for diagnosis of DMO is via clinical examination, there is considerable variability involved, and hence, this has led to the advent of more objective methods of quantifying the degree of retinal thickness, such as optical coherence tomography. Laser photocoagulation appears to be the only universally acceptable treatment of choice to date; however, this is a destructive therapy, and its side effects coupled with the suboptimal efficacy has led to the advent of potential new therapies which will undoubtedly compliment the existing approaches, in the future management of a patient with DMO.

Diabetic macular oedema: the effect of photocoagulation on fluorescein transport across the blood-retinal barrier.

BACKGROUND/AIM: The visual loss secondary to diabetic macular oedema can be controlled to some extent by photocoagulation, though the mechanism of action is largely unknown. The purpose of the present study was to quantitate the effect of photocoagulation on the blood-retinal barrier using fluorescein as a tracer of passive and active transport. METHODS: A prospective study of 46 eyes in 34 patients with clinically significant macular oedema (CSMO) examined by vitreous fluorometry before and 6 months after macular photocoagulation treatment. RESULTS: In 23 eyes CSMO was not present at follow up (responding eyes), in another 23 other eyes CSMO was still present (non-responding eyes). With reference to the presence or absence of CSMO at follow up, the passive transport (permeability) for responding eyes decreased after photocoagulation in contrast with an increase in non-responding eyes; the difference between the groups at follow up was significant (p=0.03). The active transport for responding eyes decreased slightly at follow up, while it increased for non-responding eyes; the difference between the groups at follow up was not significant (p=0.09). CONCLUSION: Following photocoagulation a reduction of diabetic macular oedema, defined as disappearance of CSMO, is paralleled by a decrease of the passive permeability while the hypothesis of an increase in the active transport from the retina to the blood could not be supported by this study.

Diabetic macular oedema: a comparison of vitreous fluorometry, angiography, and retinopathy.

AIM: To evaluate the relation between the quantitative measurement of vitreous fluorescein with fluorescein angiography and retinopathy in diabetic patients with and without clinically significant macular oedema (CSMO). METHODS: In a prospective cross sectional study, passive permeability and active, outward transport of fluorescein across the blood-retinal barrier were quantitated with vitreous fluorometry in 61 eyes from 48 patients with CSMO and 22 fellow eyes without CSMO, after exclusion of eyes with previous macular laser treatment and vitreous liquification. All patients were recruited from the university hospital's outpatient clinic. Retinopathy and fluorescein angiograms were evaluated on 60 degree photographs. RESULTS: The passive permeability in CSMO was significantly correlated with the severity of leakage on fluorescein angiograms (r=0.73), the level of retinopathy (r=0.61), and visual acuity (r=0.45). Significant differences between eyes with CSMO and eyes without CSMO were found for passive permeability (p<0.001), fluorescein leakage (p<0.001), visual acuity (p=0.02), and retinopathy (p=0.002). CONCLUSION: Passive permeability of fluorescein quantitated with vitreous fluorometry was correlated both with semiquantitative fluorescein angiography and retinopathy, and a significant increase in passive permeability was found when comparing eyes with CSMO to eyes without CSMO. No such pattern was found for the active transport indicating that passive and not the outward, active transport is the factor of most importance in the development of CSMO.

Passive permeability and outward active transport of fluorescein across the blood-retinal barrier in early ARM.

AIM: To study the passive and active transport of fluorescein across the blood-retina barrier in early age related maculopathy (ARM) (soft drusen > 63 microm, hyperpigmentation and/or hypopigmentation in patients above 50 years of age). METHODS: 15 patients and 10 healthy subjects were included. Morphological changes were graded from 30 degrees fundus photographs using a simplified version of the epidemiological ARM study group classification system. Differential vitreous spectrofluorophotometry was used to assess the transport properties of the blood-retina barrier (that is, passive permeability and unidirectional permeability caused by outward active transport from the vitreous to the blood). RESULTS: The passive permeability of the patient group was not significantly different from that of the control group. Four patients with passive permeability more than 3 SD above the mean of the control group (mean 1.8 (SD 0.7) nm/s, range 1.0-3.0 nm/s, data normally distributed) all had centrally located drusen > 500 microm and superjacent pigment clumps of 63-500 microm in diameter. There was no significant difference between the unidirectional permeabilities for the patient group and for the control group (mean 47.4 (29.3) nm/s, range 12.7-91.1 nm/s). CONCLUSION: There was no significant difference in the passive permeability and in the unidirectional permeability of fluorescein. However, the study may indicate that the combination of very large drusen and superjacent pigment clumps in ARM may be associated with a deterioration of the blood-retina barrier.

Diabetic macular edema: passive and active transport of fluorescein through the blood-retina barrier.

PURPOSE: To investigate the passive bidirectional and active outward transport of fluorescein through the blood-retina barrier (BRB) in diabetic patients with clinically significant macular edema and in healthy controls. METHODS: The passive and active transport of fluorescein through the BRB was quantitated by vitreous fluorometry. A previously developed method was used to model passive transport. A new simulation model was developed and evaluated for estimation of active transport. The study included 10 eyes of 5 healthy controls and 31 eyes of 20 diabetic patients with clinically significant diabetic macular edema (CSME) in at least one eye, totalling 25 eyes with CSME. RESULTS: Passive permeability of fluorescein was increased by a factor of 12 in eyes with edema compared to healthy controls (edema, 23.7 nm/sec; healthy subjects, 1.9 nm/sec, P < 0.01), whereas the active transport was doubled (edema, 84.1 nm/sec; healthy subjects, 43.5 nm/sec, P < 0.01). Unlike active transport, passive permeability was related to the degree of retinopathy, in that eyes with severe non-proliferative diabetic retinopathy had a passive permeability that was significantly increased compared to moderate retinopathy (32.1 nm/sec and 14.6 nm/sec, respectively, P: < 0.05). The passive movement quantitated with vitreous fluorometry was larger for diffuse and mixed leakage compared to focal (P = 0.07). CONCLUSIONS: Insofar as the movement of fluorescein can be taken as a probe for the movement of electrolytes and water, the pathogenesis of diabetic macular edema seems to involve a disruption of the BRB, presumably its inner component. The active resorptive functions of the blood-retina barrier appear to be compensatorily increased to counteract edema formation, although the increase is too small to prevent edema in the face of severe leakage through the blood-retina barrier.

Detection of shallow detachments in central serous chorioretinopathy.

PURPOSE: To study the correlation between symptoms, clinical findings, fundus photographic morphology, and optical coherence tomography in patients with symptoms of central serous chorioretinopathy, but ambiguous biomicroscopic findings and no late-phase fluorescein angiographic leakage. METHODS: Biomicroscopic slit-lamp examination, greyscale digital fundus photography in red-free illumination, fundus fluorescein angiography, optical coherence tomography, and focal retinal argon laser photocoagulation. Seven consecutive patients aged 32-69 years, of whom four received focal retinal photocoagulation treatment. RESULTS: All patients demonstrated a shallow serous detachment on optical coherence tomography. After treatment the detachment resolved, as did the relative scotoma, the prolonged dark adaptation, and the dyschromatopsia. Micropsia was markedly reduced in all, but not completely eliminated in two of the patients. CONCLUSION: Patients with central serous chorioretinopathy may have shallow foveal detachments that can only be detected by optical coherence tomography, whereas clinical and angiographic signs of detachment may be missing. Classical symptoms coupled with a normal or only mildly reduced visual acuity are highly indicative of the presence of a serous neuroretinal detachment, but fluorescein angiography is necessary to establish the diagnosis and the target for treatment.

Effects of acetazolamide on passive and active transport of fluorescein across the normal BRB.

PURPOSE: To investigate the effect of the carbonic anhydrase inhibitor acetazolamide (AZM) on passive permeability and active transport of fluorescein across the blood-retina barrier in healthy subjects. The study may have implications for the understanding of the edema-reducing effect of AZM. METHODS: The effect of AZM on the blood-retina barrier function was assessed by differential vitreous spectrofluorometry using fluorescein as a tracer. The study included fourteen healthy subjects in a randomized double-masked crossover trial with 3 days' treatment with AZM (500 mg/d) and placebo, respectively. The two examinations were separated by at least 1 week. Fluorescein concentration was determined separately from its metabolite fluorescein glucuronide. The passive permeability of fluorescein was determined by computerized modeling and curve-fitting to the preretinal curve and the plasma concentration curve obtained at 30 to 60 minutes after the injection of fluorescein. The unidirectional permeability due to outward active transport from vitreous to blood was estimated from the preretinal gradient and the plasma concentration at 7 to 10 hours after injection. RESULTS: Treatment with AZM was associated with significant increases in passive permeability and unidirectional permeability of fluorescein. For the passive permeability the increase was on average 0.3+/-0.4 nm/s (mean+/-SD; range, -0.8-1.0 nm/s), and for the unidirectional permeability the increase was on average 7.4 nm/s+/-7.0 (mean+/-SD; range, -3.3-19.0 nm/s). CONCLUSIONS: Acetazolamide caused an increase in passive permeability. Unidirectional permeability was increased by AZM, indicating a stimulation of the outward active transport of fluorescein. It has been proposed that the edema-reducing effect of AZM is due to stimulated ion and fluid removal from the retina to the choroid. The results of this study are consistent with AZM affecting the blood-retina barrier with stimulation of at least one ion transport mechanism.

The effect of acetazolamide on passive and active transport of fluorescein across the blood-retina barrier in retinitis pigmentosa complicated by macular oedema.

BACKGROUND: The carbonic anhydrase inhibitor acetazolamide (AZM) reduces macular oedema in some patients with retinitis pigmentosa. To better understand the oedema-reducing effect of AZM, the effect of AZM on passive permeability and active transport of fluorescein across the blood-retina barrier was studied in patients with retinitis pigmentosa and varying degrees of macular oedema. METHOD: The selection of patients was based on an introductory examination including vitreous fluorometry for qualitative assessment of the vitreous. Macular oedema was graded by fluorescein angiographic leakage. The effect of AZM on the transport properties of the blood-retina barrier was determined by differential spectrofluorometry, in a randomised, double-masked, cross-over study, comprising 2 weeks' treatment with AZM (500 mg/day) and 2 weeks' treatment with placebo. The penetration ratio, defined as the ratio between vitreous concentration 3 mm in front of the retina and the plasma integral, was determined for fluorescein and its metabolite fluorescein glucuronide at 30-60 min and at 120 min after fluorescein injection. Passive permeability and unidirectional permeability in the direction vitreous to blood, due to outward active transport of fluorescein, were determined in those cases where the curves for vitreous concentration of fluorescein could be fitted to a mathematical model. Visual acuity was tested by use of ETDRS standard logarithmic charts. RESULTS: Twenty-two patients volunteered to participate in the study. Signs of significant vitreous detachment/liquefaction caused the exclusion of ten patients after the introductory examination. Nine patients with approximately intact vitreous and varying degrees of oedema completed the cross-over study. AZM treatment was related to a decrease in the penetration ratio of 21% for fluorescein (P=0.01) and of 22% for fluorescein glucuronide (P=0.004). Passive permeability and unidirectional permeability were determined in seven patients. AZM caused a decrease of 27% in the passive permeability of fluorescein (from 1.1 x 10(1) nm/s, P=0.031), and a 95% increase in unidirectional permeability of fluorescein (from 1.2 x 10(2) nm/s, P=0.047). AZM led to a reduction in the grade of macular oedema as determined by fluorescein angiography in three out of seven patients. Only small improvements (< or =5 letters) in visual acuity were noted. CONCLUSION: The present study indicates that the oedema-reducing effect of AZM is due to decreased leakage and stimulated active transport across the blood-retina barrier.

Improved visual function in IDDM patients with unchanged cumulative incidence of sight-threatening diabetic retinopathy.

OBJECTIVE: To evaluate trends in visual acuity and the cumulative incidence of diabetic retinopathy in a clinic-based observational follow-up study. RESEARCH DESIGN AND METHODS: All patients visiting Hvidore Hospital in 1984 whose diagnosis of IDDM had been made before 41 years of age and between 1965 and 1979 (n = 356) were followed until 1994 or until their deaths. All patients were Caucasians and resided in Copenhagen. Patients were divided into three prevalence cohorts based on time of diabetes onset: group A, 1965-1969 (n = 113); group B, 1970-1974 (n = 130); and group C, 1975-1979 (n = 113). RESULTS: Fifteen years after diabetes onset, the visual acuity was significantly improved in patients with increasing calendar year of the disease onset. The median (interquartile range) visual acuity was 1.0 (0.8-1.0), 1.0(0.9-1.0), and 1.0 (1.0-1.0) in groups A, B, and C, respectively (P < 0.01 overall; P = 0.28 for group A vs. group B; and P < 0.01 for group A vs. group C) with 60, 66, and 93 having a visual acuity of 1.0 in groups A, B, and C, respectively. The cumulative incidence (+/-SEM), expressed as a percentage and calculated according to the life-table method, of proliferative retinopathy, maculopathy, and laser-treated retinopathy 15 years after onset of diabetes were, respectively, 13+/-3, 11+/-3, and 12+/-3 in group A; 16+/-3, 12+/-3, and 21+/-4 in group B; 11+/-3, 5+/-2, and 12+/-3 in group C, respectively (NS). The development of proliferative retinopathy was associated with the degree of retinopathy and albuminuria at baseline and the mean HbA1c during follow-up. CONCLUSIONS: The study revealed an improvement in visual acuity with increasing calendar year of diabetes onset but an unchanged cumulative incidence of diabetic retinopathy.

Blood-retina barrier permeability is independent of trace substance lipid solubility in retinitis pigmentosa and in the healthy eye.

Differential ocular spectrofluorometry was used to assess the passive permeability of the blood-retina barrier in healthy subjects and in patients with retinitis pigmentosa by determination of the rate of inward leakage of fluorescein and fluorescein glucuronide after intravenous injection of fluorescein. In five healthy subjects we found permeabilities of 1.3 (0.6-2.8) nm/s [log-mean (range)] for fluorescein and 1.3 (0.6-3.1) nm/s for fluorescein glucuronide. Six patients with retinitis pigmentosa all had a markedly increased blood-retina barrier leakage, with inward permeabilities of 8.2 (3.4-25) nm/s for fluorescein and 8.2 (5.6-27) nm/s for fluorescein glucuronide. Since no detectable difference was found between the permeabilities of the two tracers the passive permeability of the blood-retina barrier appears to be independent of the 18-fold difference in lipid solubility between the two tracers, both in retinitis pigmentosa and in healthy subjects. Presumably, the structural substrate for leakage of small hydrophilic molecules through the blood-retina barrier is a water-filled pore, since diffusion through lipid cellular membranes would favor fluorescein over its more water soluble glucuronide.

Lens autofluorescence is increased in newly diagnosed patients with NIDDM.

Lens and cornea autofluorescence has been shown to be increased in patients with insulin-dependent diabetes mellitus and to be positively correlated to glycaemic control and duration of diabetes. We have studied lens and cornea autofluorescence at the clinical onset of non-insulin-dependent diabetes mellitus (NIDDM), in comparison with age-matched subjects with normal glucose tolerance. Fourteen subjects with NIDDM diagnosed less than 6 months prior to the examination were characterised by ocular fluorometry, glycosylated hemoglobin A1c, plasma lipid status, arterial blood pressure, and an oral glucose tolerance test (OGTT). Eleven age- and gender-matched healthy subjects without a family history of diabetes and with a normal glucose tolerance underwent the same examinations. In 11 of the 14 diabetic patients lens autofluorescence was increased to levels higher than the age-related mean + 2SD of healthy subjects. For the entire study population, control and diabetic subjects, lens fluorescence was positively correlated with HbA1c (p < 0.0001, r = 0.73), fasting plasma glucose (p = 0.002, r = 0.60) and the plasma glucose level 2 h after an OGTT (p = 0.004, r = 0.55). Cornea autofluorescence was also significantly increased in the group of newly diagnosed NIDDM patients, but only 9 patients had values above the mean + 2SD of the healthy subjects. NIDDM could be detected by ocular fluorometry with a sensitivity of 79% and a specificity of 100%. We conclude that lens and cornea autofluorescence is abnormally increased in the majority of patients with newly diagnosed NIDDM. The sensitivity and specificity of the method indicate that lens fluorometry may potentially be useful for screening for undiagnosed NIDDM in the general population. Additionally, we propose that the method may be a clinically useful indicator of cumulative glycaemia and risk of development of secondary complications in patients with diabetes.

Fluorescein transport across the human blood-retina barrier in the direction vitreous to blood. Quantitative assessment in vivo.

Inward and outward movement of flourescein across the human blood-retina barrier was studied in five healthy volunteers, using a differential spectrofluorometry method that eliminates the contribution of fluorescein glucuronide to the total fluorescence in the vitreous and in plasma. The inward permeability across the blood-retina barrier, which is presumed to be passive, and the diffusion coefficient in the vitreous for fluorescein was calculated from data obtained 1 h after intravenous injection of fluorescein. The rate of elimination of fluorescein from the vitreous across the blood-retina barrier was estimated from data obtained 7 to 12 h after injection of fluorescein. The calculations were based upon the free plasma fluorescein decay curve and the preretinal fluorescein gradient in the vitreous. The mean inward permeability of fluorescein was 1.39 x 10(-7) cm/sec (range: 0.70-2.06 x 10(-7) cm/sec), whereas the mean outward permeability was 1.51 x 10(-5) cm/sec (range: 1.14-1.73 x 10(-5) cm/sec). We have thus found that the movement of fluorescein across the blood-retina barrier is highly asymmetric, the outward transport being more than 100 times faster than the passive inward leakage. This could indicate the presence of an active pumping mechanism in the blood-retina barrier, responsible for fluorescein transport in the direction from the vitreous to the blood.

Probenecid inhibition of the outward transport of fluorescein across the human blood-retina barrier.

The effect of probenecid on the outward transport of fluorescein from vitreous to blood was studied in 13 insulin-dependent diabetic patients with background retinopathy in a randomised double-masked placebo controlled cross-over study. Fluorescein and fluorescein glucuronide was separated in the vitreous and in plasma by differential spectrofluorometry. The data for fluorescein were analysed using a simplified mathematical model of the eye. The inward permeability was estimated from data obtained 1 h after injection and the outward transport from data obtained 7 h after injection. During placebo treatment the mean inward permeability was 3.75 x 10(-7) cm/sec and the mean outward permeability was 2.25 x 10(-5) cm/sec. During probenecid treatment the mean inward permeability was 3.34 x 10(-7) cm/sec and the mean outward permeability was 1.44 x 10(-5) cm/sec. Thus, we found no significant change in inward permeability (p = 0.5879), whereas a significant decrease of 36% was found in the outward permeability of fluorescein (p = 0.0171). The demonstration that the outward permeability, which is more than 100-fold higher than the inward permeability in the healthy eye, is significantly decreased by probenecid, demonstrates that active transport is involved in movement of fluorescein across the blood-retina barrier from the vitreous to the plasma.

Interferon alfa-2a modifies the course of subfoveal and juxtafoveal choroidal neovascularisation.

The first double masked placebo controlled trial of interferon alfa-2a for the treatment of overt choroidal neovascular membranes is presented. A total of 43 consecutive patients were randomised to double masked treatment with either interferon alfa-2a, 3 million IU subcutaneously three times a week or matching placebo, for a period of 8 weeks. End of study changes from baseline in distance and near visual acuity, macular visual field, contrast sensitivity, and macular morphology (fluorescein angiography) were assessed. The between group difference in distance visual acuity, the primary efficacy variable, was significant in favour of interferon alfa-2a (p = 0.023). Fluorescein angiograms, macular visual fields, and near vision all showed a trend in favour of interferon alfa-2a. It was concluded that, at the dosage used in this study, interferon alfa-2a is a reasonably well tolerated and apparently effective short term treatment of subfoveal and juxtafoveal choroidal neovascularisations.

Absence of foveal avascular zone demonstrated by laser scanning fluorescein angiography.

We present laser scanning fluorescein angiograms of abnormal foveal capillary patterns in a healthy subject and an insulin-dependent diabetic patient with mild diabetic retinopathy. In both subjects capillaries were seen to cross the central foveal area where capillaries are usually absent. The flow pattern of the foveal capillaries, which were visualised with the use of a laser scanning ophthalmoscope, was indistinguishable from that of the more peripheral capillaries, indicating that foveal vessels are functionally normal retinal capillaries. The two cases demonstrate that identification of abnormal capillary patterns induced by retinal disease such as diabetic retinopathy is made difficult by the marked interindividual variation in capillary anatomy. In prospective studies, however, the method may be capable of detecting subtle changes in early diabetic retinopathy with a high degree of sensitivity.