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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., 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.

In this retrospective comparative case series at a teaching hospital, we reviewed adult patients with rhegmatogenous retinal detachment who underwent scleral buckling surgery with external drainage of subretinal fluid performed before versus after placement of the scleral buckle. Eight eyes in each group were roughly matched for age, sex, baseline visual acuity (VA), and detachment characteristics. The complication rate was 0% for the "before" group and 37% for the "after" group (p = 0.100). In the "after" group, two eyes (25%) developed iatrogenic retinal holes and one eye (12%) developed self-limited subretinal hemorrhage during external needle drainage. The duration of surgery was significantly shorter for the "before" group (mean 89 ± 16 min) compared to the "after" group (118 ± 20 min) (p = 0.008). The primary anatomic success rate was 100% for the "before" group and 75% for the "after" group (p = 0.233). Final VA was not significantly different between the groups or from baseline. In conclusion, while limited by our small sample size, this pilot study suggests that drainage of subretinal fluid before scleral buckle placement may be safer and more efficient compared to draining after buckle placement. Initial drainage may facilitate retinochoroid apposition to allow targeted cryopexy and precise buckle placement.

Purpose: Tilted disc syndrome (TDS) may be associated with a macular serous retinal detachment (MSRD). However, ideal therapy for this complication is still unestablished yet to date. The purpose of this study is to investigate the effect of selective retina therapy (SRT) for MSRD associated with TDS. / Methods: This retrospective study included 11 eyes of 10 patients (1 male and 9 females), who were treated with SRT for MSRD associated with TDS, and observed at least 12 months after treatment....

Background : To investigate retinal thickness after selective retina therapy (SRT) for central serous chorioretinopathy (CSC) and the factors related to visual prognosis. / Methods : This retrospective study examined 23 eyes of 21 consecutive patients (17 males, 4 females) with CSC and followed-up for >6 months. A SRT (Q-switched Nd:YLF laser, 527 μm, pulse duration 1.7 μs, 30 pulses per irradiation spot with a frequency of 100 Hz) was used for the treatment. The need for re-treatment was judged every three months after the initial treatment....

The authors report a case of bilateral diffuse uveal melanocytic proliferation associated with transitional cell carcinoma of the bladder. A novel imaging finding on indocyanine green angiography of a "string of sausages" pattern in the large choroidal vessels is described. This occurs in areas of alternating retinal pigment epithelial hypertrophy and destruction, which is likely to be its cause. To the authors' knowledge, it has not been previously described.Copyright © 2019 Slack Incorporated. All rights reserved.

The authors report a case of bilateral diffuse uveal melanocytic proliferation associated with transitional cell carcinoma of the bladder. A novel imaging finding on indocyanine green angiography of a "string of sausages" pattern in the large choroidal vessels is described. This occurs in areas of alternating retinal pigment epithelial hypertrophy and destruction, which is likely to be its cause. To the authors' knowledge, it has not been previously described.Copyright © 2019 Slack Incorporated. All rights reserved.

PurposeTo describe the clinical course of a patient with persistent subretinal fluid (SRF) after primary scleral buckle surgery for a rhegmatogenous retinal detachment (RRD) repair who was subsequently treated with oral eplerenone for resolution of SRF.ObservationsA 34 year-old-male presented with a large bullous macula-involving RRD of unknown duration and underwent primary scleral buckle and retinotomy for drainage of subretinal fluid (SRF). His post-operative course was characterized by persistent macular SRF for 1.5 years with poor vision largely unchanged from his pre-operative presentation. Patient declined additional surgical treatment and opted for conservative management. Given such persistent SRF, the patient was trialed on a course of oral eplerenone 50 mg po bid. After only one month on this therapy, a marked decline in SRF was noted with near complete resolution after two months.Conclusions and importanceTo our knowledge, this is the first report of its kind to show the effectivity of oral eplerenone treatment in the reduction of SRF following retinal detachment surgery.

It is still not completely understood why some patients develop proliferative vitreoretinopathy and others do not despite extensive research on cytokine biomarkers, genetic profiles and ocular clinical risk factors. Recently, a new possible treatment target was proposed based on studies on the role of coagulation proteins in the development of PVR. While several pharmaceutical drug therapies have been proposed for PVR – targeting inflammation, proliferation and growth factors – these drugs all have potential side effects. Therefore, to optimise the benefit/risk ratio of drug therapies, it is crucial to select only those patients at high risk of developing PVR. We tested whether the oral direct thrombin inhibitor dabigatran would be a potential drug candidate for the treatment of PVR. In this respect, we tested whether oral administration would lead to measurable levels in the eye and whether dabigatran was able to oppose the effects of thrombin in an in vitro model. In addition, we tested the amount of endogenous thrombin generation and inhibition in vitreous and subretinal fluid. Furthermore, we tested the applicability of aqueous humour laser flare measurements in distinguishing between patients at high and low risk of developing PVR. Firstly, we looked at preoperative flare values and secondly at postoperative flare values. We also show that the choice of surgery might also influence postoperative inflammation and thus influences the risk of developing PVR. An aspect that has gained less attention in research is the possible influence of concomitant systemic drug

PurposeTo describe the clinical course of a patient with persistent subretinal fluid (SRF) after primary scleral buckle surgery for a rhegmatogenous retinal detachment (RRD) repair who was subsequently treated with oral eplerenone for resolution of SRF.ObservationsA 34 year-old-male presented with a large bullous macula-involving RRD of unknown duration and underwent primary scleral buckle and retinotomy for drainage of subretinal fluid (SRF). His post-operative course was characterized by persistent macular SRF for 1.5 years with poor vision largely unchanged from his pre-operative presentation. Patient declined additional surgical treatment and opted for conservative management. Given such persistent SRF, the patient was trialed on a course of oral eplerenone 50 mg po bid. After only one month on this therapy, a marked decline in SRF was noted with near complete resolution after two months.Conclusions and importanceTo our knowledge, this is the first report of its kind to show the effectivity of oral eplerenone treatment in the reduction of SRF following retinal detachment surgery.

Purpose: One of the factors that was shown to contribute to the development of proliferative vitreoretinopathy (PVR) is the coagulation factor thrombin. Therefore, a specific oral thrombin inhibitor such as dabigatran might be a possible therapeutic option. An oral drug has the advantage of patient-friendly prolonged administration in contrast to drugs that can only be applied during vitrectomy, on condition that the drug reaches the target site. We tested whether dabigatran reaches the vitreous and subretinal fluid (SRF) after a single oral dose of dabigatran. Methods: Twenty-eight patients with a retinal detachment received a single dose of 220 mg dabigatran etexilate 2–8 hr prior to surgery. During surgery, we took a blood sample and a vitreous or subretinal fluid sample. The concentration of dabigatran was measured using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Results: The dabigatran concentration between 2 and 9 hr after administration was higher in SRF than in vitreous (max 8.5 and 3.8 ng/ml). Corresponding plasma concentrations ranged from 15 to 225 ng/ml. There was a significant relationship between SRF levels and plasma levels (rs = 0.68, p = 0.014); the levels in vitreous fluid showed no such relationship (rs = 0.20, p = 0.48). In addition, we measured the vitreous concentration of a non-study patient using 150 mg dabigatran twice daily. The concentration was approximately 10 times higher than after a single dosage (25.8 ng/ml). Conclusion: We demonstrate that oral intake of dabigatran, a candidate drug to modulate PVR, results in potentially relevant intraocular concentrations. We suggest that repeated dosing may lead to higher concentrations, but this should be further explored.

Purpose To characterize perifoveal intraretinal cavities observed around full-thickness macular holes (MH) using en face optical coherence tomography and to establish correlations with histology of human and primate maculae. Design Retrospective nonconsecutive observational case series. Methods Macular en face scans of 8 patients with MH were analyzed to quantify the areas of hyporeflective spaces, and were compared with macular flat mounts and sections from 1 normal human donor eye and 2 normal primate eyes (Macaca fascicularis). Immunohistochemistry was used to study the distribution of glutamine synthetase, expressed by Müller cells, and zonula occludens-1, a tight-junction protein. Results The mean area of hyporeflective spaces was lower in the inner nuclear layer (INL) than in the complex formed by the outer plexiform (OPL) and the Henle fiber layers (HFL): 5.0 × 10-3 mm2 vs 15.9 × 10-3 mm2, respectively (P <.0001, Kruskal-Wallis test). In the OPL and HFL, cavities were elongated with a stellate pattern, whereas in the INL they were rounded and formed vertical cylinders. Immunohistochemistry confirmed that Müller cells followed a radial distribution around the fovea in the frontal plane and a "Z-shaped" course in the axial plane, running obliquely in the OPL and HFL and vertically in the inner layers. In addition, zonula occludens-1 co-localized with Müller cells within the complex of OPL and HFL, indicating junctions in between Müller cells and cone axons. Conclusion The dual profile of cavities around MHs correlates with Müller cell morphology and is consistent with the hypothesis of intra- or extracellular fluid accumulation along these cells.

AIM To describe outcomes of eyes with wet age-related macular degeneration (AMD) subdivided by lesion activity in a large multicentre cohort study. METHODS Treatment-naive eyes with subfoveal choroidal neovascularisation receiving antivascular endothelial growth factor therapy enrolled in the Fight Retinal Blindness observational study were included. Lesions were graded at each visit as active if there was intraretinal or subretinal fluid attributable to leak from choroidal neovascularisation lesion or fresh haemorrhage. Eyes were divided into four groups; based on the proportion of visits, each eye was graded as active during the first 12 months of treatment (persistent, high, moderate and low activity). RESULTS 655 eyes were included. Similar mean visual acuity changes compared with baseline were observed in all four groups at 12 months (+6.8, +8.3, +6.2 and +5.5 letters for the low, moderate, high and persistent groups, respectively; p<0.001 for each group). The mean number of injections given increased only modestly in groups with more active lesions (7.6, 7.9, 8.4 and 8.3, respectively, p=0.015). Occult and minimally classic lesions were more frequent in the more active groups (p=0.024). CONCLUSIONS Persistent activity of neovascular lesions during 12 months after starting intravitreal therapy was not associated with worse visual outcomes in this observational study of AMD.

PURPOSE: To evaluate the effect of fluid accumulation on local visual function in inflammatory cystoid-macular-edema (ICME).METHODS: This cross-sectional study applied optical-coherence-tomography over a 12×12 fovea-centered field in 50 patients with ICME and mapped the extent of fluid-filled spaces in various retinal layers, of subretinal-fluid and of diffuse-edema. Regression analysis examined effect of planimetric fluid-distribution on best-corrected-visual-acuity (BCVA) and mean microperimetric-sensitivity.RESULTS: BCVA decreased with increasing central-neuroretinal-thickness (r= 0.52, p= 0.001), total central-retinal-thickness, including subneuroretinal-fluid (r= 0.41, p= 0.006), total cystoid-and-diffuse edema-area (r= 0.35, p= 0.036) and cystoid inner-nuclear-layer area (r= 0.39, p= 0.02). Mean retinal-sensitivity decreased with increasing diffuse edema-area (r= -0.86, p<0.0001), total cystoid-and-diffuse edema-area (r= -0.54, p= 0.001), cystoid inner-nuclear-layer area (r= -0.46, p= 0.008) and cystoid ganglion-cell-layer area (r= -0.6, p=0.049), central-neuroretinal-thickness (r= -0.42, p= 0.028) and total central-retinal-thickness (r= -0.34, p= 0.039). In multivariate-analyses BCVA was best described by central-neuroretinal-thickness, duration of edema, total cystoid-and-diffuse edema-area and cystoid inner-nuclear-layer area (R(2) = 0.5, p= 0.002). Mean retinal-sensitivity was best described by diffuse edema-area, total cystoid-and-diffuse edema-area and central-neuroretinal-thickness (R(2) = 0.75, p< 0.0001). Subretinal-fluid area and cystoid outer-nuclear/Henle's layer area had no effect on either BCVA or microperimetry.CONCLUSIONS: Thickening of the neurosensory-fovea, not subfoveal-fluid, had major impact on both BCVA and retinal-sensitivity. The extent of edema in inner retinal layers also had major impact on both of these two functional parameters. Visual-impairment seems to differ depending on the layers involve

PURPOSE: To evaluate the effect of fluid accumulation on local visual function in inflammatory cystoid-macular-edema (ICME).METHODS: This cross-sectional study applied optical-coherence-tomography over a 12×12 fovea-centered field in 50 patients with ICME and mapped the extent of fluid-filled spaces in various retinal layers, of subretinal-fluid and of diffuse-edema. Regression analysis examined effect of planimetric fluid-distribution on best-corrected-visual-acuity (BCVA) and mean microperimetric-sensitivity.RESULTS: BCVA decreased with increasing central-neuroretinal-thickness (r= 0.52, p= 0.001), total central-retinal-thickness, including subneuroretinal-fluid (r= 0.41, p= 0.006), total cystoid-and-diffuse edema-area (r= 0.35, p= 0.036) and cystoid inner-nuclear-layer area (r= 0.39, p= 0.02). Mean retinal-sensitivity decreased with increasing diffuse edema-area (r= -0.86, p<0.0001), total cystoid-and-diffuse edema-area (r= -0.54, p= 0.001), cystoid inner-nuclear-layer area (r= -0.46, p= 0.008) and cystoid ganglion-cell-layer area (r= -0.6, p=0.049), central-neuroretinal-thickness (r= -0.42, p= 0.028) and total central-retinal-thickness (r= -0.34, p= 0.039). In multivariate-analyses BCVA was best described by central-neuroretinal-thickness, duration of edema, total cystoid-and-diffuse edema-area and cystoid inner-nuclear-layer area (R(2) = 0.5, p= 0.002). Mean retinal-sensitivity was best described by diffuse edema-area, total cystoid-and-diffuse edema-area and central-neuroretinal-thickness (R(2) = 0.75, p< 0.0001). Subretinal-fluid area and cystoid outer-nuclear/Henle's layer area had no effect on either BCVA or microperimetry.CONCLUSIONS: Thickening of the neurosensory-fovea, not subfoveal-fluid, had major impact on both BCVA and retinal-sensitivity. The extent of edema in inner retinal layers also had major impact on both of these two functional parameters. Visual-impairment seems to differ depending on the layers involve

Purpose: Earlier studies have revealed a decreased level of cGMP in vitreous fluid obtained from patients with a retinal detachment. To further investigate this phenomenon, we developed an experimental retinal detachment model in pigs. Methods: Experimental unilateral retinal detachments were induced in pig eyes by subretinal injection of 0.25% sodium hyaluronate. Fourteen days later the vitreous and retinas were analyzed for cGMP expression. Following enucleation, the retinas were incubated in the presence of a nonselective phosphodiesterase inhibitor (IBMX), and the particulate guanylyl cyclase stimulator atrial natriuretic peptide (ANP) or the soluble guanylyl cyclase stimulator sodium nitroprusside (SNP). cGMP was visualized in retinal wholemounts by immunochemistry combined with a computer based stereology system. cGMP levels in vitreous were determined by ELISA. Results: The mean vitreous cGMP level in pig eyes with a retinal detachment (1.45 pmol/ml) was significantly lower compared to the mean level of cGMP in healthy pig eyes (4.61 pmol/ml; p= 0.028 was considered significant). In the inner retina, ANP as well as SNP induced cGMP immunoreactivity in both detached and healthy retinas. After incubation with ANP, cGMP could also be detected in the outer nuclear layer of the detached retina, whereas this was not the case in the normal retina. Conclusions: Experimental retinal detachment in the pig eye leads to a decrease of cGMP levels in vitreous similar to that observed in clinical studies. This model may be helpful to analyze the mechanisms involved in cGMP dynamics following retinal detachment.