Evaluating the Efficacy and Safety of Aflibercept Biosimilar (P041) Compared with Originator Product in Patients with Neovascular Age-Related Macular Degeneration.

OBJECTIVE: To assess the noninferiority of biosimilar aflibercept (P041, CinnaGen) to the originator aflibercept (AFL, Regeneron) in terms of efficacy, safety, and immunogenicity. DESIGN: This was a phase Ш, 52-week, multicenter, randomized, double-masked, and active control trial involving eyes in a 1:1 ratio. SUBJECTS: Patients with active subfoveal choroidal neovascularization secondary to age-related macular degeneration randomized into the 2 groups of P041 and AFL. METHODS: Patients received an injection of aflibercept every 4 weeks for 3 doses, followed by administration every 8 weeks up to week 48. MAIN OUTCOME MEASURES: The primary outcome was the noninferiority analysis of eyes maintaining vision at week 52. Secondary outcomes included the changes in visual acuity and retinal thickness, safety evaluation, and immunogenicity during the study. RESULTS: In total, 168 eyes of 168 patients were included. At week 52, the proportion of patients maintaining vision was 94.44% in the P041 group compared with 94.52% in the AFL group. The 95% confidence interval (CI) for the difference of maintaining vision from baseline did not exceed the predefined noninferiority margin of 10% (difference, -0.0008; 95% CI, -0.074 to 0.074; P = 0.98). Secondary outcomes indicated similar results in both arms (all P > 0.05). Safety measured outcomes and immunogenicity were similar between the 2 study groups. CONCLUSIONS: Biosimilar aflibercept was noninferior to AFL in eyes with neovascular age-related macular degeneration. Other efficacy and safety findings also indicated the similarity of 2 products. FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Assessment of area and structural irregularity of retinal layers in diabetic retinopathy using machine learning and image processing techniques.

Diabetes retinopathy prevention necessitates early detection, monitoring, and treatment. Non-invasive optical coherence tomography (OCT) shows structural changes in the retinal layer. OCT image evaluation necessitates retinal layer segmentation. The ability of our automated retinal layer segmentation to distinguish between normal, non-proliferative (NPDR), and proliferative diabetic retinopathy (PDR) was investigated in this study using quantifiable biomarkers such as retina layer smoothness index (SI) and area (S) in horizontal and vertical OCT images for each zone (fovea, superior, inferior, nasal, and temporal). This research includes 84 eyes from 57 individuals. The study shows a significant difference in the Area (S) of inner nuclear layer (INL) and outer nuclear layer (ONL) in the horizontal foveal zone across the three groups (p < 0.001). In the horizontal scan, there is a significant difference in the smoothness index (SI) of the inner plexiform layer (IPL) and the upper border of the outer plexiform layer (OPL) among three groups (p < 0.05). There is also a significant difference in the area (S) of the OPL in the foveal zone among the three groups (p = 0.003). The area (S) of the INL in the foveal region of horizontal slabs performed best for distinguishing diabetic patients (NPDR and PDR) from normal individuals, with an accuracy of 87.6%. The smoothness index (SI) of IPL in the nasal zone of horizontal foveal slabs was the most accurate at 97.2% in distinguishing PDR from NPDR. The smoothness index of the top border of the OPL in the nasal zone of horizontal slabs was 84.1% accurate in distinguishing NPDR from PDR. Smoothness index of IPL in the temporal zone of horizontal slabs was 89.8% accurate in identifying NPDR from PDR patients. In conclusion, optical coherence tomography can assess the smoothness index and irregularity of the inner and outer plexiform layers, particularly in the nasal and temporal regions of horizontal foveal slabs, to distinguish non-proliferative from proliferative diabetic retinopathy. The evolution of diabetic retinopathy throughout severity levels and its effects on retinal layer irregularity need more study.

Pachychoroid neovasculopathy versus macular neovascularization in age-related macular degeneration with and without shallow irregular pigment epithelial detachment.

To compare the choroidal neovascular features of individuals with pachychoroid neovasculopathy (PNV) and neovascular age-related macular degeneration (nAMD) with and without shallow irregular pigment epithelial detachment (SIPED). Using optical coherence tomography angiography, the choroidal neovascular complexes of 27 patients with PNV, 34 patients with nAMD and SIPED, and 15 patients with nAMD without SIPED were analyzed with FIJI and AngioTool software. PNV compared to nAMD with SIPED had a greater vessel percentage area (P = 0.034), junction density (P = 0.045), average vessel length (P < 0.001), and fractal dimension (P < 0.001). PNV, compared to nAMD without SIPED, had a greater total vessel length (P = 0.002), total number of junctions (P < 0.001), junction density (P = 0.034), and fractal dimension (P = 0.005). nAMD with SIPED, compared to nAMD without SIPED, had greater vessel area, total number of junctions, total vessel length, and average vessel length (all P values < 0.001). Patients with nAMD plus SIPED and individuals with nAMD without SIPED have similar fractal dimension values (P = 0.703). Biomarkers of choroidal neovascular complexity, such as fractal dimension, can be used to differentiate PNV from nAMD with or without SIPED.

CNV-Net: Segmentation, Classification and Activity Score Measurement of Choroidal Neovascularization (CNV) Using Optical Coherence Tomography Angiography (OCTA).

This paper aims to present an artificial intelligence-based algorithm for the automated segmentation of Choroidal Neovascularization (CNV) areas and to identify the presence or absence of CNV activity criteria (branching, peripheral arcade, dark halo, shape, loop and anastomoses) in OCTA images. Methods: This retrospective and cross-sectional study includes 130 OCTA images from 101 patients with treatment-naïve CNV. At baseline, OCTA volumes of 6 × 6 mm2 were obtained to develop an AI-based algorithm to evaluate the CNV activity based on five activity criteria, including tiny branching vessels, anastomoses and loops, peripheral arcades, and perilesional hypointense halos. The proposed algorithm comprises two steps. The first block includes the pre-processing and segmentation of CNVs in OCTA images using a modified U-Net network. The second block consists of five binary classification networks, each implemented with various models from scratch, and using transfer learning from pre-trained networks. Results: The proposed segmentation network yielded an averaged Dice coefficient of 0.86. The individual classifiers corresponding to the five activity criteria (branch, peripheral arcade, dark halo, shape, loop, and anastomoses) showed accuracies of 0.84, 0.81, 0.86, 0.85, and 0.82, respectively. The AI-based algorithm potentially allows the reliable detection and segmentation of CNV from OCTA alone, without the need for imaging with contrast agents. The evaluation of the activity criteria in CNV lesions obtains acceptable results, and this algorithm could enable the objective, repeatable assessment of CNV features.

Microvascular and structural analysis of the retina and choroid in heart failure patients with reduced ejection fraction.

This cross-sectional study was designed to assess alterations of choroidal and retinal microvasculature in patients with Heart Failure with Reduced Ejection Fraction (HFrEF) and compare them with a normal age and sex-matched population. Fifty-two eyes of 26 patients with HFrEF (left ventricular ejection fraction [LVEF] < 40%) and 64 eyes of 32 healthy individuals were considered as the patient and the control groups, respectively. We found no statistically significant differences in age-adjusted mean central macular thickness (CMT), superficial or deep retinal capillary plexus vascular densities, and choriocapillaris flow (CC flow) density between the HFrEF group and the normal controls, with the exception of the parafoveal mean superficial capillary plexus vascular density (P = 0.023), which remained statistically significant after adjusting for age (P = 0.034). The patients with HFrEF had a significantly lower subfoveal choroidal thickness (SFCT) than the normal subjects (264 ± 82 vs 313 ± 72; P = 0.009), and the difference was still statistically significant after age adjustment (P = 0.026). Although choroidal vascularity index (CVI) was lower in the HFrEF group than in the control group, the difference was not statistically significant before and after age adjustment (73.45 ± 6.67 vs 75.77 ± 5.92; P = 0.118 and P = 0.096, respectively). In conclusion, in patients with HFrEF, we observed a reduction in parafoveal retinal VD in the superficial capillary plexus, as well as SFCT, but no significant change in CVI, CMT, or CC flow density.

Automated machine learning-based classification of proliferative and non-proliferative diabetic retinopathy using optical coherence tomography angiography vascular density maps.

PURPOSE: The study aims to classify the eyes with proliferative diabetic retinopathy (PDR) and non-proliferative diabetic retinopathy (NPDR) based on the optical coherence tomography angiography (OCTA) vascular density maps using a supervised machine learning algorithm. METHODS: OCTA vascular density maps (at superficial capillary plexus (SCP), deep capillary plexus (DCP), and total retina (R) levels) of 148 eyes from 78 patients with diabetic retinopathy (45 PDR and 103 NPDR) was used to classify the images to NPDR and PDR groups based on a supervised machine learning algorithm known as the support vector machine (SVM) classifier optimized by a genetic evolutionary algorithm. RESULTS: The implemented algorithm in three different models reached up to 85% accuracy in classifying PDR and NPDR in all three levels of vascular density maps. The deep retinal layer vascular density map demonstrated the best performance with a 90% accuracy in discriminating between PDR and NPDR. CONCLUSIONS: The current study on a limited number of patients with diabetic retinopathy demonstrated that a supervised machine learning-based method known as SVM can be used to differentiate PDR and NPDR patients using OCTA vascular density maps.

Pars plana vitrectomy combined with phacoemulsification versus pars plana vitrectomy only for treatment of phakic rhegmatogenous retinal detachment: a systematic review and meta-analysis.

PURPOSE: To compare the visual, refractive, and anatomical outcomes and incidence of complications between combined pars plana vitrectomy and phacoemulsification (phacovitrectomy) versus pars plana vitrectomy (PPV-only) in phakic eyes with rhegmatogenous retinal detachment (RRD). METHODS: Two independent reviewers searched MEDLINE, Cochrane Central, and Web of Science to identify relevant articles. Prospective or retrospective studies comparing PPV-only and phacovitrectomy for RRD were included. Recruited studies provided information about at least anatomical success or refractive outcomes. Meta-analysis was performed for single surgery success rate, final best-corrected visual acuity (BCVA), postoperative complications, mean predicted refractive error, and mean absolute predicted refractive error. RESULTS: Seven studies (788 eyes) were selected, including two clinical trials and five retrospective comparative case series. The single surgery success rate was similar in PPV-only and phacovitrectomy groups (risk ratio [RR] = 1.02; 95% confidence interval [CI] 0.95-1.10; P = 0.57). Mean final BCVA was significantly better in the PPV-only group than the phacovitrectomy group (MD = 0.06; 95% CI 0.00-0.12; P = 0.04). The risk of epiretinal membrane formation was significantly higher in eyes that underwent phacovitrectomy than PPV-only (RR = 2.85; 0.95% CI 1.5-5.41; P = 0.001). Phacovitrectomy group showed a more myopic final mean predicted refractive error than PPV-only group (MD = -0.31; 95% CI -0.55--0.07; P = 0.01). CONCLUSION: There was no significant difference between the two groups regarding the anatomical outcome. Slightly better visual and refractive results were observed in the PPV-only group. However, the results should be interpreted with caution as the majority of included studies were low-quality retrospective studies.

Evaluation of the additive effect of interferon α 2b with monthly intravitreal injection of bevacizumab in refractory diabetic macular edema.

BACKGROUND: To evaluate the additive effect of topical or sub-tenon injection of interferon (IFN)-α 2b in the treatment of refractory diabetic macular edema. METHODS: In this prospective study patients with center-involved DME who were unresponsive to 3 monthly consecutive IVB injections were recruited. Patients were divided into three groups: group1, received IFN- α 2b topical drop at a dose of 1mIU/ml four times a day for 3 months. Group 2, received a single sub-tenon injection of 1mIU/ml IFN- α 2b at the enrollment. Group 3 received artificial tears four times a day for 3 months (control group). All groups received three consecutive monthly IVB injections and were evaluated monthly up to 1 month following the last IVB injection. RESULTS: In this study, 59 eyes of 35 patients with refractory DME were assessed. The final follow-up showed that although CMT decreased in all groups, only patients in Group 2 had statistically significant lower CMT compared to their baseline values (change in CMT: - 117 ± 213 µm; p-value = 0.025). Comparison of CMT changes between three groups showed no statistically significant difference, although it was higher in group 2 (change in CMT: - 117 ± 213 µm (Group2) vs. - 49 ± 173 (Group 1) vs. - 36 ± 86 (Group 3); p-value = 0.085). Considering eyes with baseline CMT > 400 µm, sub-tenon injection of IFN α2b led to a significant reduction of CMT at the first month and final follow-up visit (CMT change: - 166 ± 210, - 145 ± 231 µm; p-value = 0.018 and 0.035, respectively). In this subgroup, eyes in Group 2 had lower CMT at the first month following treatment in comparison with the control group (CMT: 444 ± 123 µm vs. 544 ± 96 µm, p-value = 0.042). Alterations of CDVA were not statistically significant among groups, although patients in Group 1 had a significant improvement in vision at second and last follow up (CDVA change: - 0.23 ± 0.39, - 0.20 ± 0.43 logMAR; p-value = 0.030 and 0.010, respectively). CONCLUSIONS: In short term, Sub-tenon injection of IFN might have an additive anatomical effect in eyes with refractory DME. Validation of this observation requires further prospective controlled studies.

Flat irregular pigment epithelial detachment over time and outcome of different treatment regimens.

To present long-term visual and structural outcome of treatment in two forms of flat irregular pigment epithelial detachment (FIPED): avascular (aFIPED) and vascularized (vFIPED) in eyes within pachychoroid spectrum. Prospective interventional case series. FIPED were classified into two subgroups; aFIPED and vFIPED based on OCTA. aFIPED underwent PDT, and vFIPED underwent either PDT, IVB, or combination of PDT&IVB. Vision, subretinal or intraretinal fluid, and choroidal biomarkers such as choroidal thickness, area, choroidal vascular index (CVI), and PED area were measured at baseline and last follow-up. Fifteen eyes with aFIPED were followed for a mean of 14.7 ± 10.8 months. Their vision improved, (0.44 ± 0.37-0.33 ± 0.40 LogMAR, p = 0.009) with significant reduction of fluid, choroidal area, thickness, PED area and increase in CVI. Twenty eyes with vFIPED were followed for a mean of 16.5 ± 8.2 months. The same pattern of choroidal alterations without visual improvement was observed in eyes underwent PDT alone. Combination therapy resulted in improvement of vision (0.38 ± 0.10-0.23 ± 0.17 LogMAR, p = 0.006) with reduction of choroidal area and thickness, with an increase in CVI. IVB alone could not change vision or choroidal structure. Single session PDT may lead to sustained visual improvement and structural change in eyes with aFIPED. Combination of PDT and IVB may be a better choice in eyes with vFIPED.

Treatment of Inflammatory Macular Hole: Case Series and Review of Literature.

PURPOSE: To present the success rate of nonsurgical management of full-thickness inflammatory macular hole (IMH). METHOD: Retrospective case series of five patients with IMH. RESULT: Five eyes from five patients with IMH enrolled in the current case series. All five eyes had successful closure with corticosteroid in the form of topical, periocular, or intravitreal injections. Systemic immunomodulatory treatment was employed for two patients, in addition to local therapy. For local therapy, one patient received topical eye drops, subtenon injection of corticosteroid, and intravitreal injection of combination of corticosteroid and anti-VEGF was performed in two patients. The closed macular hole reopened in one patient after two years, which required pars plana vitrectomy and anatomical and visual success achieved. CONCLUSION: Inflammatory macular holes can be closed with non-surgical interventions, although reopening may occur which requires surgery.

Alterations in choroidal vascular parameters following panretinal photocoagulation using enhanced-depth imaging optical coherence tomography in diabetic retinopathy.

PURPOSE: To investigate the alteration of choroid in patients with very severe non-proliferative diabetic retinopathy (NPDR) or early proliferative diabetic retinopathy (PDR) following panretinal photocoagulation (PRP). METHODS: Thirty-nine eyes of 21 patients with very severe non-proliferative diabetic retinopathy (NPDR) (19 eyes) and early proliferative diabetic retinopathy (PDR) (20 eyes) were recruited. Enhanced-depth imaging optical coherence tomography at baseline, 1, and 6 months after PRP was employed to measure choroidal parameters including total choroidal area (TCA) and choroidal vascular index (CVI). RESULTS: In eyes with very severe NPDR, subfoveal TCA decreased non-significantly at month 1, which increased significantly at month 6 (539 ± 131µm2, 502 ± 134µm2, and 598 ± 168µm2 at baseline and months 1 and 6, respectively; P = 0.003). Subfoveal CVI increased at month 1 and then decreased at month 6 (68.25 ± 3.05, 69.74 ± 3.62, and 67.84 ± 1.77 at baseline and months 1 and 6, respectively; P < 0.001). A reverse pattern occurred in eyes with early PDR, a non-significant increase in TCA at month 1 followed by a decrease at month 6 (497 ± 95µm2, 514 ± 133µm2, and 425 ± 95µm2 at baseline and months 1 and 6, respectively; P = 0.011). CVI decreased at month 1 and remained relatively stable at month 6 (69.34 ± 3.11, 68.33 ± 3.41, and 68.50 ± 5.04 at baseline, and months 1 and 6, respectively; P = 0.023). Alteration of choroidal thickness was not statistically significant in both groups. CONCLUSION: Eyes with very severe NPDR and early PDR exhibit a reverse pattern regarding choroidal indices after PRP.

Transscleral vs transpupillary diode laser photocoagulation for the treatment of zone II type 1 retinopathy of prematurity: Anatomical and refractive outcomes.

PURPOSE: To compare the anatomical and refractive outcomes of transscleral diode versus transpupillary laser photocoagulation for the treatment of zone II type 1 retinopathy of prematurity (ROP). METHODS: In this prospective comparative interventional case series, infants with type 1 ROP in zone II were assigned to either transpupillary or transscleral laser based on the surgeons' expertise area. The rate of regression, need for retreatment, and structural and biometric outcomes at month 6 were evaluated and compared between the two treatment groups. RESULTS: In total, 209 eyes were enrolled; 145 eyes of 77 infants and 64 eyes of 33 infants and were in transscleral and transpupillary groups, respectively. There was no significant difference in baseline characteristics between the groups. There was no significant difference in retreatment rates (1.6% vs. 3.4%; P = 0.669) and progression to stage 4 (1.6% vs. 2.8%; P = 0.999) between the transpupillary and transscleral groups, respectively. At month 6, the mean spherical equivalent was 0.31 ± 3.57 and 0.44 ± 2.85 diopters, and the axial length was 18.28 ± 6.22 and 18.36 ± 6.87 mm in the transpupillary and transscleral groups, respectively, without a significant difference between groups. There was no significant difference in the rate of myopia (43.8% vs. 33.8%; P = 0.169) and high myopia (4.7% vs. 4.8%; P = 0.965) in transpupillary and transscleral groups at month 6. CONCLUSION: The transpupillary and transscleral laser photocoagulation routes are both effective in the treatment of zone II type 1 ROP and show no significant differences in anatomical or refractive outcomes in relation to the route chosen.

Sickle Cell Trait Presenting as Unilateral Proliferative Retinopathy and Macular Thinning in a Pregnant Woman.

BACKGROUND: To report a case of a pregnant woman with sickle cell trait (SCT) who presented with unilateral proliferative sickle cell retinopathy. Case Presentation. A 26-year-old otherwise healthy pregnant woman presented with the complaint of visual loss in her left eye. The funduscopic examination showed vitreous hemorrhage, sea fan neovascularization, and pale optic disc. Optical coherence tomography revealed macular inner retinal layer thinning and foveal splaying (saucerization of the foveal pit). The investigations, including hemoglobin electrophoresis, verified the diagnosis of sickle cell trait. Blood pressure, fasting blood glucose tests, and tuberculin skin tests were normal. We treated the patient by peripheral retinal photocoagulation over the area of nonperfusion. CONCLUSION: Even though the sickle cell trait is generally considered as a milder form of sickle cell disease without severe retinal manifestations, pregnancy should be considered as a trigger that can induce proliferative changes and foveal splaying in this group of patients.

Macular Infarction following Intravitreal Clindamycin Injection : A Case Report.

PURPOSE: To report a case of Toxoplasma retinochoroiditis that was complicated by macular infarction following intravitreal clindamycin injection. METHODS: A 32-year-old otherwise healthy woman with the diagnosis of reactivation of Toxoplasma retinochoroiditis in her right eye, underwent intravitreal clindamycin injection. Shortly after injection, the visual acuity deteriorated, and the fundus examination revealed an extensive area of macular necrosis accompanied by vascular occlusion. RESULTS: The patient was observed. Unfortunately, the condition did not improve over time and resulted in a large area of retinal atrophy. CONCLUSION: Macular infarction should be considered a rare but disastrous complication that can result in severe, irreversible visual loss.

Evaluation of radiation maculopathy after treatment of choroidal melanoma with ruthenium-106 using optical coherence tomography angiography.

BACKGROUND: To assess the impact of brachytherapy on macular microvasculature utilizing optical coherence tomography angiography (OCTA) in treated choroidal melanoma. METHODS: In this retrospective observational case series, we reviewed the recorded data of the patients with unilateral extramacular choroidal melanoma treated with ruthenium - 106 (106Ru) plaque radiotherapy with a follow-up period of more than 6 months. Automatically measured OCTA retinal parameters were analysed after image processing. RESULTS: Thirty-one eyes of 31 patients with the mean age of 51.1 years were recruited. Six eyes had no radiation maculopathy (RM). From 25 eyes with RM, nine eyes (36%) revealed a burnout macular microvasculature with imperceptible vascular details. Twenty-one non-irradiated fellow eyes from the enrolled patients were considered as the control group. Foveal and optic disc radiation dose had the highest value to predict the burnout pattern (ROC, AUC: 0.763, 0.727). Superficial and deep foveal avascular zone (FAZ) were larger in irradiated eyes in comparison to non-irradiated fellow eyes (1629 µm2 vs. 428 µm2, P = 0.005; 1837 µm2 vs 268 µm2, P = 0.021; respectively). Foveal and parafoveal vascular area density (VAD) and vascular skeleton density (VSD) in both superficial and deep capillary plexus (SCP and DCP) were decreased in all irradiated eyes in comparison with non-irradiated fellow eyes (P < 0.001). Compared with non-irradiated fellow eyes, irradiated eyes without RM had significantly lower VAD and VSD at foveal and parafoveal DCP (all P < 0.02). However, these differences at SCP were not statistically significant. CONCLUSION: The OCTA is a valuable tool for evaluating RM. Initial subclinical microvascular insult after 106Ru brachytherapy is more likely to occur in DCP. The deep FAZ area was identified as a more critical biomarker of BCVA than superficial FAZ in these patients.

Choroidal features in flat irregular pigment epithelial detachment associated with Chronic central serous chorioretinopathy: Avascular versus vascularized.

PURPOSE: To investigate the differences in the choroidal biomarkers between two forms of flat irregular pigment epithelial detachment (FIPED): avascular (aFIPED) and vascularized (vFIPED) in eyes with chronic central serous chorioretinopathy (CSC). MATERIALS AND METHODS: Enhanced depth imaging optical coherence tomography (EDI-OCT) was done in eyes with FIPED correlated to chronic CSC, fellow eyes, and also in healthy eyes from gender- and age-matched subjects. Eyes with FIPED were classified into two subgroups based on optical coherence tomography angiography (OCTA) findings: vFIPED and aFIPED. Different choroidal biomarkers such as subfoveal choroidal thickness (SFCT), total choroidal area (TCA), and choroidal vascular index (CVI) were compared between the groups. RESULTS: Forty-four eyes from 42 patients with chronic CSC and FIPED along with 40 eyes from 20 healthy subjects were included. OCTA identified vascularization in 14 eyes in the FIPED group (31.8%). Mean SFCT was higher in the FIPED group compared to two other groups (p = 0.005). In comparison to patients with aFIPED, patients with vFIPED had lower SFCT (p = 0.003) and higher CVI (p = 0.020) based on multivariate analysis. CONCLUSIONS: It seems that measurement of CVI along with SFCT may help to differentiate aFIPED from vFIPED in patients with CSC. Further longitudinal studies would be required to confirm the clinical significance of these findings.

Closantel Retinal Toxicity: Case Report and Literature Review.

A 57-year-old shepherd was referred with a 2-week history of decreased visual acuity in both eyes. Optical coherence tomography (OCT) (Heidelberg Engineering GmbH, Heidelberg, Germany) revealed diffuse outer nuclear layer hyperreflectivity and indistinguishable external limiting membrane and ellipsoid zone. The patient announced to us that he took two 500 mg of closantel tablets (15.15 mg/kg) three days before the initiation of visual problems for sore throat as an antibiotic. Electroretinography displayed severely attenuated responses in both eyes. We decided to admit the patient with the presumed diagnosis of closantel retinal toxicity and treated him with intravenous methylprednisolone 1 g per day and intravenous erythropoietin 10000 IU twice a day, and reevaluation of the patient proved no change in his visual acuity on the third day of admission. Closantel is a veterinary drug with serious side effects in the human retina and central nervous system even in previously reported doses. Public awareness and appropriate drug labeling about its side effects could prevent accidental toxicity. OCT is a noninvasive and rapid diagnostic modality that should be done in suspected toxic retinopathy.

Autosomal Recessive Bestrophinopathy: Clinical and Genetic Characteristics of Twenty-Four Cases.

BACKGROUND: To describe ocular manifestations, imaging characteristics, and genetic test results of autosomal recessive bestrophinopathy (ARB). The study design is an observational case series. METHODS: Forty-eight eyes of 24 patients diagnosed with ARB underwent complete ophthalmic examinations including refraction, anterior and posterior segment examination, enhanced depth imaging optical coherence tomography (EDI-OCT), fluorescein angiography (FA), electroretinography (ERG), and electrooculography (EOG). Optical coherence tomography angiography (OCTA) and BEST1 gene sequencing were performed in selected patients. RESULTS: The age at onset was 4-35 years (mean: 18.6 years). The male-to-female ratio was 0.45. All patients were hyperopic, except one with less than one diopter myopia. EOG was abnormal in 18 cases with near-normal ERGs. Six patients did not undergo EOG due to their young age. Eighteen patients (75%) had a thick choroid on EDI-OCT, of which three had advanced angle-closure glaucoma, 15 patients were hyperopic, and eight of them had more than four diopters hyperopia in both eyes. Macular retinoschisis was observed in 46 eyes of 23 patients (95%) with cysts mostly located in the inner nuclear layer (INL) to the outer nuclear layer (ONL). Of the 18 patients who underwent FA, mild peripheral leakage was seen in eight eyes of four patients (22%). Subfoveal choroidal neovascularization (CNV) was seen in three eyes of two patients (6%) that responded well to intravitreal bevacizumab (IVB). Seven mutations of the bestrophin-1 (BEST1) gene were found in this study; however, only two of them (p.Gly34 = and p.Leu319Pro) had been previously reported as the cause of ARB based on ClinVar and other literature studies. CONCLUSIONS: ARB can be presented with a wide spectrum of ocular abnormalities that may not be easily diagnosed. Pachychoroid can occur alongside retinal schisis and may be the underlying cause of angle-closure glaucoma in ARB. Our study also expands the pathogenic mutation spectrum of the BEST1 gene associated with ARB.

Intraocular Injection of StivantⓇ (A Biosimilar to Bevacizumab): A Case Series.

PURPOSE: To report the results of intravitreal injection of a bevacizumab biosimilar called StivantⓇ. METHODS: This prospective interventional case series was conducted on eyes with neovascular age-related macular degeneration (nAMD), retinal vein occlusion (RVO), and diabetic macular edema (DME). StivantⓇ was injected in three consecutive months and changes in best-corrected visual acuity (BCVA) and central macular thickness (CMT) were measured at baseline and monthly up to one month after the third injection. RESULTS: Three hundred and eighty-five eyes with DME (234 eyes, 61%), nAMD (87 eyes, 22%), and macular edema secondary to RVO (64 eyes, 17%) were enrolled. The mean ± standard deviation age of the patients was 61.7 ± 7.20 years. The mean BCVA and CMT changed from 0.63 ± 0.3 to 0.51 ± 0.3 LogMAR (P = 0.12 ) and from 420.4 ± 47.3µm at baseline to 316.7 ± 50.6 µm (P < 0.001) in the DME group; from 0.79 ± 0.3 to 0.68 ± 0.3 LogMAR (P = 0.19) and from 376.1 ± 31.7 µm to 303 ± 31.3 µm (P = 0.019) in the nAMD group; and from 0.81 ± 0.4 to 0.63 ± 0.4 LogMAR (P = 0.05) and from 424.21 ± 18 µm to 303.4 ± 18.8 µm (P < 0.001) in the RVO group, respectively. CONCLUSION: Our limited experience showed that the intravitreal injection of StivantⓇ was well tolerated. Although the results of this case series showed relative improvement in CMT one month after the last injection of StivantⓇ, BCVA improvement was statistically significant only in the RVO group. This would be essential to design a randomized clinical trial to evaluate the non-inferiority of StivantⓇ in comparison to bevacizumab.