Topical non-steroidal anti-inflammatory drugs for central serous chorioretinopathy: A systematic review and meta-analysis.

Central serous chorioretinopathy (CSC) is a prevalent exudative maculopathy and the ongoing verteporfin shortage restricts current treatment possibilities. Topical non-steroidal anti-inflammatory drugs (NSAID) have previously been proposed as a treatment for CSC, although its exact efficacy remains unclear. In this systematic review and meta-analysis, we outlined the efficacy of topical NSAIDs for the treatment of CSC. We searched 11 literature databases on 13 December 2022, for any study describing topical NSAID treatment for CSC. Thirteen eligible studies were included with a total of 1001 eyes of 994 patients with CSC. Six studies were case reports, two were cohort studies and five were non-randomized comparative studies. Where specified, topical NSAIDs used were bromfenac 0.09%, diclofenac 0.1%, ketorolac 0.4% and 0.5%, pranoprofen 0.1%, and nepafenac 0.1% and 0.3%. Studies were predominantly of cases with acute CSC and several case studies reported treatment outcomes simultaneously with discontinuation of corticosteroid use, which complicated treatment evaluation. Meta-analyses of comparative studies revealed a statistically significant but clinically irrelevant best-corrected visual acuity improvement of -0.04 logMAR (95% CI: -0.07 to -0.01 logMAR; p = 0.01) at 1-month follow-up, which became statistically insignificant at 3-month follow-up (-0.03 logMAR; 95% CI: -0.06 to 0.003 logMAR; p = 0.08). Further, we found no benefit in complete subretinal fluid resolution at 1-month follow-up (OR: 1.20; 95% CI: 0.81-1.76; p = 0.37) or 3-month follow-up (OR: 1.17; 95% CI: 0.86 to 1.59; p = 0.33). Taken together, available evidence does not support the use of topical NSAIDs for the treatment of CSC.

Prevalence of geographic atrophy in Nordic countries and number of patients potentially eligible for intravitreal complement inhibitor treatment: A systematic review with meta-analyses and forecasting study.

We systematically reviewed the literature on the prevalence of geographic atrophy (GA) in Nordic populations, conducted meta-analyses on age-stratified estimates, and calculated current and future number of patients and those potentially eligible for intravitreal complement inhibitor treatment. We followed the PRISMA guidelines, and our protocol was registered in PROSPERO. Ten databases were searched on 22 April 2023 for population-based studies of GA prevalence. Based on clinical descriptive analyses of GA and eligibility criteria of the phase III studies for intravitreal pegcetacoplan (complement C3 and C3b inhibitor), we were able to calculate the proportion of patients with GA potentially eligible for therapy. Finally, we extracted population data for Nordic countries (Denmark, Finland, Iceland, Norway, and Sweden) from Eurostat, applied prevalence statistics to the extracted census and forecasting data to estimate the number of patients with GA, and then applied the proportion eligible for intravitreal pegcetacoplan therapy. We identified six studies with a total of 10 159 individuals. Prevalence of GA was estimated to 0.4% (95% confidence intervals [CI]: 0.2%-0.8%), 1.5% (95% CI: 0.7%-2.6%), and 7.6% (95% CI: 4.6%-11.3%) for individuals aged 60-69, 70-79, and 80+ years, respectively. In Nordic countries, we estimate a total of 166 307 individuals with GA in 2023, increasing to 277 893 in 2050. Of these, 90 803 individuals in 2023, increasing to 151 730 in 2050, are potentially eligible for intravitreal complement inhibitor treatment. Considering these large numbers, our study highlights the importance of this topic in the coming years and its potential to significantly impact our clinical practice, organization, and staffing.

Scientific Literature Database Coverage of Randomized Clinical Trials for Central Serous Chorioretinopathy.

BACKGROUND: Systematic literature searches are the cornerstone of systematic reviews. In this study, we evaluated database coverage of randomized clinical trials for central serous chorioretinopathy (CSC). METHODS: We searched 12 databases (BIOSIS Previews, CINAHL, the Cochrane Central, Current Contents Connect, Data Citation Index, Derwent Innovations Index, EMBASE, KCI-Korean Journal Database, MEDLINE, PubMed, SciELO Citation Index, and Web of Science Core Collection) on 10 April 2023 for randomized clinical trials for CSC. After identifying all eligible studies across all databases, we investigated the coverage of these studies within each database, including the coverage of any combination of two databases. RESULTS: The 12 databases yielded 848 records for screening, of which 76 were randomized clinical trials for CSC. No single database provided full coverage. The most comprehensive coverage was provided by EMBASE (88%), the Cochrane Central (87%), and PubMed (75%). A combined search in the Cochrane Central and PubMed led to complete coverage (100%) while reducing the number of records for screening from 848 to 279. CONCLUSIONS: Systematic review search design should include multiple databases. For randomized clinical trials for CSC, the combination of the Cochrane Central and PubMed provides an excellent balance between coverage and workload.

Is Erythrocyte Sedimentation Rate Necessary for the Initial Diagnosis of Giant Cell Arteritis?

Giant cell arteritis (GCA) is an ophthalmological emergency that can be difficult to diagnose and prompt treatment is vital. We investigated the sequential diagnostic value for patients with suspected GCA using three biochemical measures as they arrive to the clinician: first, platelet count, then C-reactive protein (CRP), and lastly, erythrocyte sedimentation rate (ESR). This retrospective cross-sectional study of consecutive patients with suspected GCA investigated platelet count, CRP, and ESR using diagnostic test accuracy statistics and odds ratios (ORs) in a sequential fashion. The diagnosis was established by experts at follow-up, considering clinical findings and tests including temporal artery biopsy. A total of 94 patients were included, of which 37 (40%) were diagnosed with GCA. Compared with those without GCA, patients with GCA had a higher platelet count (p < 0.001), CRP (p < 0.001), and ESR (p < 0.001). Platelet count demonstrated a low sensitivity (38%) and high specificity (88%); CRP, a high sensitivity (86%) and low specificity (56%); routine ESR, a high sensitivity (89%) and low specificity (47%); and age-adjusted ESR, a moderate sensitivity (65%) and moderate specificity (65%). Sequential analysis revealed that ESR did not provide additional value in evaluating risk of GCA. Initial biochemical evaluation can be based on platelet count and CRP, without waiting for ESR, which allows faster initial decision-making in GCA.

Optical Coherence Tomography of Peripapillary Vessels in Giant Cell Arteritis and Ischaemic Ocular Disease.

With normal retinal blood flow, cross-sectional optical coherence tomography (OCT) of retinal vessels shows a structured intravascular reflectivity profile, resembling a 'figure-of-8'. Altered profiles have been reported in vascular occlusive and haematological diseases. Giant cell arteritis (GCA) can cause visual loss, usually due to anterior ischaemic optic neuropathy (AION) or retinal artery occlusion. Our aim was to extend the assessment of OCT vascular profiles to patients with suspected GCA and to determine if any abnormalities were related to GCA per se or to ischaemic ocular conditions. This nested retrospective study included 61 eyes of 31 patients (13 with GCA). Six eyes had arteritic and seven eyes non-arteritic AION, three eyes had non-arteritic retinal artery occlusion, 11 eyes had other ocular conditions and 34 were unaffected control eyes. For each eye the appearance of structured intravascular profiles on peripapillary OCT was graded as present, partial, absent or uncertain. Non-presence of structured intravascular profiles was more frequent in AION and retinal artery occlusion than in other ocular conditions or unaffected eyes (Fisher's test, p = .0047). Based on follow-up of 25 eyes, reflectivity profiles normalised in three out of four eyes after 85 (35-245) days. Vessel profiles were not associated with GCA (p = .32) and were similar in arteritic and non-arteritic AION (p = .66). In conclusion, absence of structured intravascular reflectivity profiles may be a marker of acute ischaemia in the anterior optic nerve or inner retina. However, it did not seem specific for GCA. The prognostic value warrants further studies.

Retinal Vessel Diameter Changes in Relation to Dark Adaptation and Acute Hyperglycemia.

The purpose of this experimental clinical study was to assess the effects of dark adaptation and acute changes in glycemia on retinal vessel diameters in men. The study included 14 patients (mean age 63 years, range 48-74 years) with type 2 diabetes mellitus and minimal or no diabetic retinopathy. Retinal vessel diameters were assessed using infrared photography before and after dark adaptation, first while fasting and then at peak hyperglycemia during an oral glucose tolerance test (OGTT). Dark adaptation was accompanied by retinal vasodilatation, both during fasting (mean glycemia 7.6 ± 1.7 mM) and postprandial hyperglycemia (15.7 ± 4.2 mM). When fasting, the increase in vein diameter during dark adaptation was 2.0% after 20 min (P=0.018) and 2.9% after 40 min (P=0.010). When subjects were hyperglycemic, the increase during dark adaptation was 2.8% for retinal vein diameters (P=0.027) and 2.0% for retinal artery diameters after 20 min (P=0.002) and 1.7% for retinal artery diameters after 40 min (P=0.022). For identical conditions of light/dark adaptation, retinal vessels were dilated when subjects were fasting compared to postprandial hyperglycemia. Thus, darkness and fasting were both associated with retinal vasodilation in this short-term experiment in patients with type 2 diabetes. Future studies should determine whether both the stimuli of vasodilation lead to retinal hyperperfusion, which would support that they may be involved in the aggravation of diabetic retinopathy.

Baseline haemoglobin A1c influences retinal function after long-term insulin pump therapy.

PURPOSE: The purpose of the study was to characterize the long-term effect of insulin pump therapy (CSII) on electroretinography and dark adaptometry and to examine the influence of baseline glycaemic control on retinal function in patients with type 1 diabetes mellitus. METHODS: This prospective observational extension study enrolled 13 patients out of 17 who completed a primary 1-year study of the effect of CSII on retinal function. Twelve patients were still on CSII at follow-up. The extension study included a single examination 3.5 years (range 3.0-4.0 years) after initiation of CSII of one study eye per patient. Procedures included full-field electroretinography (ERG), dark adaptometry, optical coherence tomography, and fundus photography. RESULTS: Mean ERG amplitudes 3.5 years after initiation of CSII were 15-43 % lower than at baseline (all p < 0.05) and 21-45 % lower than after 1 year on CSII. The mean rate of dark adaptation had returned to baseline after a transient 13 % (p = 0.0024) acceleration at the 1-year visit. Reduction of ERG amplitudes between 1 and 3.5 years was statistically associated predominantly with baseline haemoglobin A1c (HbA1c) ≥ 8.7 % and, to a smaller extent, with HbA1c reductions larger than 1.9 % after initiation of CSII. No significant changes in ERG amplitudes were found in patients with baseline HbA1c < 8.7 % and HbA1c reductions smaller than 1.9 %. CONCLUSIONS: Deterioration of subclinical retinal function from 1 to 3.5 years after initiation of CSII was associated predominantly with poorer metabolic control before initiation of CSII. Analyses of retinal function may supplement structural and morphological characteristics in the study of diabetic complications.

Retinal vascular and structural dynamics during acute hyperglycaemia.

PURPOSE: To compare retinal vascular dynamics during acute hyperglycaemia in patients with type 2 diabetes and healthy volunteers. METHODS: Twenty-one patients with type 2 diabetes and 27 healthy controls were examined with fundus photographic measurement of retinal vessel diameters, retinal oximetry, macular perfusion velocities and optical coherence tomographic measurement of subfoveal choroidal thickness every 30 min during a 3-hr 75 g oral glucose tolerance test (OGTT). Patients paused antidiabetic therapy for 1 week prior to the OGTT. RESULTS: Plasma glucose (PG) and fluctuations in PG were larger in patients with diabetes (p < 0.0001). PG increased significantly 30 min after ingestion of glucose (p < 0.0001 in both groups). With a delay of 0-120 min, the PG increase was followed by increased retinal arterial oxygen saturations and arteriovenous oxygen saturation differences, narrowed retinal veins and increased arteriovenous diameter ratios. No effect of age, gender or diabetes status was observed. Choroidal thickness was transiently reduced in controls and unchanged in patients with diabetes (p = 0.021). Macular perfusion velocities increased after 150 min in patients with diabetes but not in controls (arterial p = 0.059; venous p = 0.16). Higher age and diabetes tended to be associated with higher retinal arterial oxygen saturation. CONCLUSION: The transition from fasting to acute hyperglycaemia is followed, with a delay of up to 2 hr, by retinal vascular changes, notably increased oxygen extraction, suggesting an effect of secondary metabolic changes. Retinal responses were similar in patients with type 2 diabetes and controls despite differences in glucose levels. It is necessary to standardize measurement conditions in studies of retinal physiology.