Sub-optimal gain in vision in retinal vein occlusion due to under-treatment in the real world: results from an open-label prospective study of Intravitreal Ranibizumab.

BACKGROUND: Macular edema secondary to retinal vein occlusion (RVO) is an important cause of loss of vision. Intravitreal injections (IVI) of anti-vascular endothelial growth factor (VEGF) are the standard of care in this disease, as shown in numerous randomized controlled trials. The purpose of this study was to study the efficacy and safety of ranibizumab, an anti-VEGF agent, in the real-world setting. METHODS: This was 48 weeks, open-label, prospective, multicentre, observational study. Patients diagnosed with ME secondary to RVO were treated with IVI of Ranibizumab 0.5 mg in real-world conditions. Efficacy was measured by improvement seen in best-corrected visual acuity (BCVA) in terms of Early Treatment of Diabetic Retinopathy Study (ETDRS) Letter Scores and change in central retinal thickness (CRT) measured by optical coherence tomography. RESULTS: One hundred eyes of 100 patients (79 with branch retinal vein occlusion and 21 with central retinal vein occlusion) were recruited in the study. The mean (standard deviation, SD) BCVA was 52.8 (21.99) letters at baseline and 62.3 (24.40) letters at week 48. From baseline, there was a significant improvement in BCVA by 7.7 letters (p = 0.001) at 48 weeks. The mean (SD) of CRT was 479.9 (216.25) µm at baseline and it decreased significantly to 284.9 (171.35) µm at week 48 (p < 0.001). During the study period, the average number of intravitreal injections was 3.5 per patient. There was no report of endophthalmitis in any eye. CONCLUSIONS: Ranibizumab is well tolerated and effective in treating macular edema secondary to RVO in real-world clinical settings. However, there is under-treatment compared to controlled clinical trials, and the gain in vision is sub-optimal with under-treatment. TRIAL REGISTRATION: Clinical Trials Registry - India: CTRI/2015/07/005985 .

External limiting membrane angle as a composite predictive index for post-operative ELM closure in full thickness macular holes.

AIM: To evaluate pre-operative qualitative and quantitative parameters of external limiting membranes (ELM) and other associated full thickness macular holes (FTMH) features and their predictive values for post-operative anatomical and functional outcomes. METHODS: This was a retrospective study of 48 eyes that underwent vitrectomy with internal limiting membrane (ILM) peeling for FTMH and had type 1 closure. All subjects underwent optical coherence tomography (SDOCT, Heidelberg, Spectralis), and the eyes were divided into complete ELM closure (CEC) and incomplete ELM closure (IEC) groups based on the post-operative OCTs within 2 months, and ROC curves were used to estimate which of the pre-operative parameters could best predict eyes falling in the CEC group. RESULTS: The mean pre-op ELM defect was smaller in CEC group (594 µm vs 1126 µm, p < 0.001) and so was the pre-op EZ defect (770 µm vs 1186 µm, p = 0.001). The mean ELM angle also was smaller in the CEC group (51.6° vs 102.5°, p < 0.001) and so was the mean hole inlet distance (353 µm vs 596 µm, p < 0.001). The post-operative ELM defect showed a significant negative correlation with visual acuity (r = - 0.319; p = 0.027). The ELM angle was most predictive with an AUROC of 0.958, and a cut-off of 68.3° had a sensitivity of 90% and a specificity of 89%. CONCLUSION: Our study introduces a novel parameter called the ELM angle and proves that it has a high sensitivity and specificity in predicting complete ELM reformation post-surgery in the short term as well as the long term.

Spectral domain optical coherence tomography study of macular microhole morphology and its correlation with vitreomacular interface abnormalities.

To describe the demographic, clinical and optical coherence tomography (OCT) characteristics of macular microholes and to determine if the size or character of the microholes has any correlation with vitreomacular interface abnormalities. Case records of 46 eyes of 39 consecutive patients with diagnosed macular microholes were reviewed as a non-interventional retrospective case study. Demographic and clinical features were noted from the detailed case records. Spectral domain OCT images were analysed for microhole and retinal characteristics. SPSS 16.0 was used for statistical analysis. Main outcome measure was the presence of vitreomacular interface abnormalities in large and small macular microholes. Of 39 patients, 21 were male and 18 were female. Most of these patients (56.4 %) presented with visual complaints. Clinically, the commonest feature was a 'red spot' at the fovea on indirect ophthalmoscopy (25 of 44 eyes; 54.3 %). Mean logMAR vision was 0.117 (±SD 0.21). 34 (76.08 %) eyes exhibited a photoreceptor loss, 38 eyes (82.6 %) had lamellar tissue defects involving layers posterior to the outer nuclear layer. The difference between means of the groups with and without vitreomacular interface abnormalities was analysed using the unpaired t test. The presence of vitreomacular interface abnormalities was significantly associated with the size of the microhole, with larger microholes being more likely to have vitreomacular interface abnormalities than smaller ones (p < 0.05). We concluded that there was a positive correlation between the size of the microhole and the presence of vitreomacular interface abnormalities. Visual acuity had no correlation with the size of the microhole; functional vision was generally well preserved in the affected eyes.

Innovator Versus Biosimilar Ranibizumab in Polypoidal Choroidal Vasculopathy: Real-World Evidence.

INTRODUCTION: To analyze the efficacy and safety profile of the intravitreal ranibizumab biosimilar molecule, Razumab® (Intas Pharmaceuticals, Ahmedabad, India; BRm; Razumab®) and the innovator ranibizumab drug (IRm; LUCENTIS®) in Indian patients with polypoidal choroidal vasculopathy (PCV) under real-world conditions. METHODS: This was a retrospective study of treatment-naïve and previously treated PCV eyes undergoing intravitreal therapy with either BRm or IRm from January 2019 to September 2020 as three loading doses followed by a pro-re-nata (PRN) regimen. Changes in the best-corrected visual acuity (BCVA), subretinal fluid (SRF), intraretinal fluid (IRF), SRF height, and subfoveal choroidal thickness (SFCT) and the safety profiles were assessed at weeks 12, 24, and 52, respectively. RESULTS: A total of 22 eyes received IRm and 19 eyes underwent BRm therapy, respectively. Both the groups were comparable in age (P = 0.41) and gender distribution, although the BRm arm had significantly more eyes that were previously treated (P < 0.00001) with a greater median number of injections (P < 0.0001). At week 52, both groups had similar gains in visual acuity (P = 0.19), SRF resolution (P = 0.8), IRF resolution (P = 0.47), and SRF height (P = 0.71). The IRm eyes exhibited a significant improvement in BCVA (P = 0.001) at all visits with a greater mean number of injections (IRm: 5.41 ± 0.94; BRm: 4 ± 1.45; P = 0.0004), while the BRm eyes showed a similar increase in BCVA but did not reach statistical significance until week 52. The SFCT decreased significantly in the BRm arm at week 52 (P = 0.045). One eye (5.26%) in the BRm arm experienced mild anterior uveitis, which was treated with topical corticosteroids. In either arm, no other ocular or systemic adverse effects were observed. CONCLUSIONS: Our real-world data demonstrated the ranibizumab biosimilar Razumab to have comparable visual acuity outcomes to the innovator ranibizumab molecule with an adequate safety profile in the management of PCV. Although these encouraging results support its use as a viable alternative to the innovator molecule, further prospective studies in a diverse patient population are needed to validate our findings.

Comparing Three Models of Community-Based Diabetic Retinopathy Screening, Treatment, and Awareness Creation Services in Southern India / South Kerala.

Background: The aim of the study was to evaluate the effectiveness of three models of diabetic retinopathy (DR) screening from an economic perspective and their effectiveness in awareness creation, screening, and ability to deliver treatment. Materials and Methods: Analysis of a prospective screening program for diabetes mellitus and DR in South Kerala was done. Three models were created: Model 1: blood screening camp, Model 2: comprehensive eye camp, and Model 3: institution-based screening camp. Results: Forty-seven camps were conducted in Model 1, 438 in Model 2, and 18 in Model 3. Of 94,993 people screened, the percentage of diabetes was 17.4. Of the diabetics screened, the percentage of retinopathy was 22.8. Model 1 was most economically viable to detect a large number of new diabetics. Model 2 was more economically challenging but had the best overall pickup rate for new DR patients. Model 3 had a lesser pickup of new DR patients. Conclusion: Model 1 is effective in picking up new diabetics but poor for DR screening. Model 3 is cost-efficient with very high DR detection rates. Cost-effective screening activities and service delivery are best achieved through a well-planned Model 2 camp which has the best overall detection rate for DR.

Rapid Onset Neovascular Glaucoma due to COVID-19-related Retinopathy.

Aim: To present a case of rapid onset on neovascular glaucoma following the Coronavirus disease 2019 (COVID-19). Background: COVID-19 has various ocular manifestations such as conjunctivitis, uveitis, retinal vasculitis, and so on. However, to date, the development of neovascular glaucoma has not been reported in COVID-19. Case description: A 50-year-old male with a history of COVID-19 3 weeks ago presented with left eye (OS) central retinal artery occlusion (CRAO) and right eye (OD) cystoid macular edema with disc and microvascular leakage on multimodal imaging. After being managed conservatively for 2 weeks, the patient developed OD neovascular glaucoma with intraocular pressure (IOP) of 44 mm Hg and angle neovascularization (NVA) on gonioscopy. The patient was started on topical antiglaucoma medications (AGM) with panretinal photocoagulation (PRP) and responded well with complete regression of NVA, CME, and normal IOP after 3 weeks. Conclusion: This is the first reported case of rapid onset of NVG secondary to COVID-19-induced retinal vasculitis. COVID-19-associated prothrombotic state with secondary retinal vascular involvement can potentially trigger such NVG. Such NVG responds well with topical AGM and PRP therapy. Clinical significance: Given the global COVID-19 pandemic, it is imperative to be vigilant regarding the various vision-threatening manifestations associated with the disease such as the NVG. How to cite this article: Soman M, Indurkar A, George T, et al. Rapid onset Neovascular Glaucoma due to COVID-19-related Retinopathy. J Curr Glaucoma Pract 2022;16(2):136-140.

Late-onset Boucher-Neuhäuser Syndrome (late BNS) associated with white-matter changes: a report of two cases and review of literature.

Boucher-Neuhäuser syndrome (BNS) is rare autosomal recessive disease, characterised by cerebellar ataxia, hypogonadotropic hypogonadism and chorio-retinal degeneration. The authors report a family (brother, 22 years and sister 24 years) with late-onset BNS (>10 years). They had subnormal intelligence; the cerebellar ataxia was progressive over 2 years with early functional dependence. Puberty was attained in a brother with testosterone injections, while the girl had primary amenorrhoea. There were no associated visual complaints. They both had diffuse periventricular white-matter hyperintensities in cerebral cortex and diffuse cerebellar atrophy in the MRI.

De-novo multilayering in fibrovascular pigment epithelial detachment.

This study describes the occurrence of multilayered pigment-epithelial detachment (MLPED) as a De-novo phenomenon (DN-MLPED) and compare the features with multi-layering secondary to chronic anti-vascular endothelial growth factor (anti-VEGF) therapy (s-MLPED). We did a retrospective evaluation of spectral-domain optical coherence tomography (SD-OCT) features, treatment-profile, and visual-acuity (VA) outcomes in eyes with MLPED. Out of 17 eyes with MLPED, 7 eyes had DN-MLPED and 10 eyes had s-MLPED. There was no significant difference in baseline and final VA between the groups. At the final visit, no significant visual improvement was noted in both the groups, although a possible trend towards an improvement was seen in DN-MLPED eyes while the s-MLPED demonstrated a declining trend (DN-MLPED-LogMAR-BCVA: Baseline = 0.79 [∼ 20/123] ± 0.91; Final = 0.76 [∼ 20/115] ± 0.73; p = 0.87; s-MLPED-LogMAR BCVA: Baseline = 0.43 [∼ 20/54] ± 0.68; Final = 0.94 [∼ 20/174] ± 0.71; p = 0.06). Moreover, after presentation, the median number of injections in DN-MLPED eyes were significantly lower compared to s-MLPED eyes (DN-MLPED:4; s-MLPED:12; p = 0.03) (Median follow-up: DN-MLPED = 26 months; s-MLPED = 54 months; p = 0.15). Subretinal hyperreflective-material (SHRM) deposition heralded the onset of multilayering and was seen to progress in all DN-PED eyes and 1/4 eyes of s-MLPED. To conclude, MLPED is a unique form of cicatrizing fibrovascular-PED which can evolve denovo too. Long-standing disease with intermittent or low-grade activity can potentially explain this unique phenomenon. With fewer anti-VEGF therapy, the de-novo MLPED eyes show more visual stability as compared to s-MLPED eyes.

Progression of Subclinical Pachychoroid Neovasculopathy to an Active Neovascularization in the Presence of Acquired Vitelliform Lesions.

We describe a unique case of bilateral acquired vitelliform lesions in a 67-year-old-female with pachychoroid associated with subretinal fluid in the right eye (OD) and a nonexudative choroidal neovascular membrane (CNVM) in the left eye (OS). Multimodal imaging performed at baseline and over the ensuing two years showed an increase in the OS vitelliform lesions with a concurrent transformation of quiescent CNVM to an exudative form. Further studies are warranted to gain better insight into the etiopathogenesis of these vitelliform lesions in pachychoroid and their potential role in instigating CNVM activation.

Intraretinal Cysts in Macular Hole: A Structure-Function Correlation Based on En Face Imaging.

PURPOSE: To characterize retinal micromorphic changes on en face optical coherence tomography (OCT) and to determine their role in pathogenesis and visual outcomes in macular hole (MH) surgery. PATIENTS AND METHODS: This is a retrospective, interventional, consecutive case series of 28 eyes undergoing successful MH surgery. Pre- and post-operative en face OCT were manually segmented, and the correlation between parameters such as MH basal diameter and minimal inlet area, area of cyst in inner plexiform layer (IPL) and outer plexiform layer (OPL), percentage of cyst in IPL and OPL, and amount of ellipsoid zone (EZ) defect and external limiting membrane (ELM) defect was performed. Their relationship with visual acuity (VA) outcomes (Group 1: ≥20/60; 14 eyes; Group 2: <20/60; 14 eyes) was also evaluated. RESULTS: A significant positive correlation was noted between the cyst area in OPL and IPL (r=0.768; p<0.001), which in turn were positively correlated with the basal diameter of the MH in all eyes. The cyst area was significantly more in IPL as compared to OPL in all eyes (p=0.049) and in group 2 (p=0.03) but not in group 1 (p=0.62). As compared to group 2, eyes in group 1 had significantly better pre- and post-operative VA, and significantly smaller basal diameter, minimal inlet area, area of cyst in IPL and OPL, and amount of defect in the ELM (postoperative) and EZ (pre- and post-operative), respectively. CONCLUSION: An increase in the basal diameter of the MH is associated with a simultaneous congruous enlargement of the area of cyst in IPL and OPL. Based on these imaging findings, we propose that the possible rationale for the origin of these intraretinal cysts could be a breakdown in the physiological retinal pigment epithelium (RPE) pump due to the anatomical separation of the neurosensory retina from the underlying RPE, ie, "RPE contact loss" theory.

Idiopathic lenticular surface neovascularization: An unusual presentation.

PURPOSE: To present a case of posterior lenticular surface neovascularization in the absence of any ocular or systemic pathology. OBSERVATIONS: A 29-year-old asymptomatic male was detected with the right eye (OD) posterior lenticular surface neovascularization extending for six-clock hours in the temporal portion along with the presence of mild posterior capsular haze. His best-corrected visual acuity was 20/25 in OD and 20/20 in the left eye (OS). No additional abnormality was identified in the remainder of the OD anterior segment and the fundus respectively. OS evaluation was unremarkable. OD imaging including B-scan ultrasonography and ultrasound biomicroscopy (UBM) were essentially normal. The anterior segment optical coherence tomography (AS-OCT) thickened lens capsule with a dense hyperreflective layer adhered to its posterior surface and separating from the capsule in the periphery. Few hyperreflective dots were visible posterior to the ciliary body although no CB thickening was noted. No systemic abnormality was detected. The patient is being managed conservatively and has shown no signs of progression of the neovascularization over six months. CONCLUSIONS AND IMPORTANCE: This is the first reported case of an isolated idiopathic posterior lenticular surface neovascularization occurring in an otherwise healthy patient. Although an unspecified breach in the posterior capsule or undetermined cyclitis can trigger such neovascularization, further histopathological studies of the capsular biopsy and ciliary body can provide better insight into its etiopathogenesis. Additionally, considering the asymptomatic nature of the condition, these patients can be observed and closely monitored.

Plume Sign in the Deturgescence of Macular Cysts - A Novel OCT Finding.

AIM: To describe a novel OCT finding called "Plume sign" in macular cysts. METHODS: Case records of five cases were retrospectively reviewed. Their case history and imaging findings on spectral domain optical coherence tomography (SD-OCT, Spectralis, Heidelberg, Germany) have been described. RESULTS: We observed five cases which had a solitary cyst foveal or parafoveal in location, was unique due to the presence of a plume-shaped internal substance, was treated with topical NSAIDs and was associated with good visual outcomes. We observed three cardinal events; firstly, retinal thickening followed by the formation of a foveal or parafoveal solitary cyst. Secondly, a vertical expansion of the solitary cysts in an inverted flask-shaped configuration associated with splitting of the retinal layers suggested by a hyper-reflective line and/or a hyporeflective cleft in the outer nuclear layer. Thirdly and finally, a breach of the outer retina with involvement of the external limiting membrane (ELM) and ellipsoid zone (EZ) with an exit trail of proteinaceous material through the defect in the shape of a plume of smoke hyper-reflective on OCT followed by deturgescence of the cyst. CONCLUSION: In conclusion, we describe the "plume" sign - a novel OCT finding is cysts and provide a possible pathogenic hypothesis.

Macular morphometrics in foveal displacement following full thickness macular hole surgery.

Purpose: To investigate if the ratio of the preoperative nasal and temporal "arms" of the macular hole (MH) can have a predictive value in the magnitude of foveal displacement postoperatively. Methods: This is retrospective interventional case series of eyes of 40 patients with full-thickness macular hole (FTMH), which underwent vitrectomy with internal limiting membrane (ILM) peeling and had Type 1 closure.All subjects underwent pre and postoperative optical coherence tomography (OCT, Heidelberg, Spectralis, Germany). Their pre and postoperative foveo-papillary distance (FPD) was measured and the magnitude of shift was calculated. The nasal and temporal arm lengths, their ratio (N/T ratio), and the hole base diameter were measured in the preoperative OCTs.The main outcome measure was the correlation of the N/T ratio with the postoperative foveal displacement. Results: We observed that in 25% (n = 10) the fovea shifted temporally; in 75% (n = 30) it shifted nasally. The shift did not show a significant correlation with either N/T ratio (r = 0.155, P = 0.34) or with base diameter (r = -0.008, P = 0.961). The odds ratio (OR) was 4.92 (P = 0.04) and the relative risk (RR) was 3.12 (P = 0.039) for a longer temporal segment to predict a temporal shift. Conclusion: Both nasal and temporal shifts are possible after successful hole closure and temporal shifts can also occur in a significantly high proportion of patients. Temporal shifts are more likely in eyes with a longer temporal segment.

Retinal vasospastic phenomenon in a known case of systemic lupus erythematosus.

Retinal vasospasm was visualized in a young female; a known case of systemic lupus erythematosus (SLE) retinopathy with unaffected vision. The fundus fluorescein angiogram showed a cyclical filling and emptying of the retinal vessels which was suggestive of vasospasm and a retinal Raynaud's-like phenomenon with no obvious perfusion deficit. There was retinal thinning involving the superficial layers that was seen on optical coherence tomography (OCT), capillary fill voids on OCT angiography, and retinal surface undulations seen on multicolor imaging. All imaging was performed on Spectralis (Heidelberg, Germany).

Familial exudative vitreoretinopathy (FEVR). Clinical profile and management.

PURPOSE: To report our experience with the diagnosis and management of Familial Exudative Vitreoretinopathy (FEVR) in a predominantly older Indian population.. METHODS: This prospective interventional non-comparative case series included 38 patients of FEVR and their 23 family members. The diagnosis was established by clinical examination, fluorescein angiography and family screening. Prophylactic photocoagulation/cryotherapy or surgical treatment was done depending on the severity of the disease. RESULTS: The mean age of the patients was 23.6 years. The fundus/fluorescein angiographic findings in 116 eyes of our 61 patients (6 eyes phthisical) were as follows: forty eight (41.4%) eyes had only peripheral avascular zone, 8 (6.9%) eyes had peripheral new vessels, and 35 (30.1%) eyes had retinal detachments (RD)--10 (8.6%) exudative, 5 (4.3%) tractional and 20 (17.2%) rhegmatogenous. Prophylactic photocoagulation or cryotherapy was done in 34 eyes for retinal holes, local exudative detachments and bleeding new vessels. All the eyes retained stable vision over a mean follow-up of 16 months. Only 14 RDs were suitable for surgery: scleral buckling, vitrectomy or both. The reattachment rate was 85.7% (12 of 14) and the best-corrected visual acuity (BCVA) improved to 5/60 or better in 50% of these eyes over a 2-year follow-up. CONCLUSIONS: FEVR appears to be more common than reported. Timely diagnosis and intervention is essential in view of the lifelong progression of the disease, late exacerbations, frequent involvement of family members, and poor surgical results. A high index of suspicion, family screening and early prophylaxis are recommended to prevent avoidable blindness from this underdiagnosed disease.

Macular ischaemia as a marker for nephropathy in diabetic retinopathy.

PURPOSE: To determine whether diabetic macular ischaemia is associated with ischaemic heart disease (IHD), hyperlipidaemia, hypertension (HTN) and nephropathy. METHODS: Prospective case-control study from January to December 2001, involving 102 type 2 diabetic patients (aged 40-80 years), 59 with unilateral / bilateral macular ischaemia and 43 concurrent controls. Diabetic retinopathy was graded and macular ischaemia assessed by fundus examination, central fundus photography and fluorescein angiography. Systemic examination and laboratory investigations were done to evaluate systemic diseases. The associations were analysed by Chi-square test and Student's t-test. The significance of the variables as independent risk factors was tested by logistic regression analysis. RESULTS: Macular ischaemia was not associated with IHD (P=1.00); HTN (P=1.00) and hyperlipidaemia (P=0.30). Nephropathy was significantly associated with macular ischaemia (P=0.025; odds ratio [OR]: 2.62; 95% confidence interval [CI]: 1.16-5.9). The association remained significant after controlling for age, gender, duration of diabetes, severity of retinopathy, HTN, IHD and hyperlipidaemia. Further, the association with nephropathy was not affected by the presence of macular isachaemia in one or both the eyes (P=0.39). CONCLUSION: Macular ischaemia may serve as a marker for nephropathy in type 2 diabetes mellitus irrespective of the severity of retinopathy.

Morphological patterns of indirect choroidal rupture on spectral domain optical coherence tomography.

PURPOSE: To evaluate the morphological types of indirect choroidal rupture (ICR) using spectral domain optical coherence tomography (SD-OCT). METHODS: This was a prospective interventional study of 18 eyes of 18 patients who presented with a history of blunt ocular trauma resulting in choroidal rupture. All patients underwent detailed ophthalmic evaluation and SD-OCT examination. RESULTS: Mean age of the patients was 32±9.6 years. Morphologically, two types of choroidal rupture were seen on SD-OCT. The first type seen (Type 1 ICR) was a forward protrusion of the retinal pigment epithelium-choriocapillaris (RPE-CC) layer with an acutely angled pyramid or dome shape. This was associated with either a small loss of continuity of the retinal pigment epithelium layer or elevated RPE-CC projection accompanied by a significant quantity of subretinal hemorrhage. The second type observed (Type 2 ICR) was a larger area of disruption of the RPE-CC layer, photoreceptor inner segment/outer segment junction, and external limiting membrane, with a posteriorly directed concave contour depression at that area and downward sliding of tissues into the defect. At presentation, ten eyes were observed to have Type 1 ICR and eight to have Type 2 ICR. Of the 18 eyes, one with Type 1 ICR and two with Type 2 ICR developed choroidal neovascularization (16.6%). CONCLUSION: Two distinct tomographic patterns of choroidal ruptures were identified on SD-OCT, which may allow ruptures to be classified into two morphological types. There are morphometric and clinical differences between the two types, which may help to prognosticate visual outcome and anticipate complications following choroidal ruptures.