Risk factors for the time to development of retinopathy of prematurity in premature infants in Iran: a machine learning approach.

BACKGROUND: Retinopathy of prematurity (ROP), is a preventable leading cause of blindness in infants and is a condition in which the immature retina experiences abnormal blood vessel growth. The development of ROP is multifactorial; nevertheless, the risk factors are controversial. This study aimed to identify risk factors of time to development of ROP in Iran. METHODS: This historical cohort study utilized data from the hospital records of all newborns referred to the ROP department of Farabi Hospital (from 2017 to 2021) and the NICU records of infants referred from Mahdieh Hospital to Farabi Hospital. Preterm infants with birth weight (BW) ≤ 2000 g or gestational age (GA) < 34 wk, as well as selected infants with an unstable clinical course, as determined by their pediatricians or neonatologists, with BW > 2000 g or GA ≥ 34 wk. The outcome variable was the time to development of ROP (in weeks). Random survival forest was used to analyze the data. RESULTS: A total of 338 cases, including 676 eyes, were evaluated. The mean GA and BW of the study group were 31.59 ± 2.39 weeks and 1656.72 ± 453.80 g, respectively. According to the criteria of minimal depth and variable importance, the most significant predictors of the time to development of ROP were duration of ventilation, GA, duration of oxygen supplementation, bilirubin levels, duration of antibiotic administration, duration of Total Parenteral Nutrition (TPN), mother age, birth order, number of surfactant administration, and on time screening. The concordance index for predicting survival of the fitted model was 0.878. CONCLUSION: Our findings indicated that the duration of ventilation, GA, duration of oxygen supplementation, bilirubin levels, duration of antibiotic administration, duration of TPN, mother age, birth order, number of surfactant administrations, and on time screening are potential risk factors of prognosis of ROP. The associations between identified risk factors were mostly nonlinear. Therefore, it is recommended to consider the nature of these relationships in managing treatment and designing early interventions.

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.

Automated assessment of the smoothness of retinal layers in optical coherence tomography images using a machine learning algorithm.

Quantifying the smoothness of different layers of the retina can potentially be an important and practical biomarker in various pathologic conditions like diabetic retinopathy. The purpose of this study is to develop an automated machine learning algorithm which uses support vector regression method with wavelet kernel and automatically segments two hyperreflective retinal layers (inner plexiform layer (IPL) and outer plexiform layer (OPL)) in 50 optical coherence tomography (OCT) slabs and calculates the smoothness index (SI). The Bland-Altman plots, mean absolute error, root mean square error and signed error calculations revealed a modest discrepancy between the manual approach, used as the ground truth, and the corresponding automated segmentation of IPL/ OPL, as well as SI measurements in OCT slabs. It was concluded that the constructed algorithm may be employed as a reliable, rapid and convenient approach for segmenting IPL/OPL and calculating SI in the appropriate layers.

Assessment of retinal and choroidal vessel density and nerve fibre layer thickness changes after orbitotomy in patients with severe non-active thyroid orbitopathy: a prospective study.

PURPOSE: To evaluate the optical coherence tomography angiogram changes in non-active severe thyroid-related ophthalmopathy patients after cosmetic bone decompression. METHODS: Eighteen patients (25 eyes) with severe not active not compressive (NANC) TED who were candidates for decompression surgery for cosmetic reasons were included in this study, and a 3 × 3 mm macular scan was used to measure vessel density and RNFL thickness. Whole macular vessel density in its superficial, deep and choriocapillaris layers was evaluated. The following data were extracted for each of layers: superior and inferior hemispheres, fovea, parafoveal vessel density, its superior and inferior hemispheres, and temporal, superior, nasal and inferior quadrant. RESULTS: The mean RPC increased postoperatively, which was statistically significant in small vessels of peripapillary area (p-value = 0.045). The mean RNFL thickness decreased after surgery and it was statistically significant in the peripapillary (p-value = 0.032) and Inferior-Hemifield area (p-value = 0.036). The choriocapillaris changes were significant in Superior-Hemifield (p-value = 0.031) and Fovea (p-value = 0.03). CONCLUSION: Thyroid-associated orbitopathy patients have a tendency to decrease vascular density and correlated with disease activity more than stage of orbitopathy. There was not a strong and even discrepant result in linkage of RNFL thickness and other optic nerve function tests and TED patient status and it is needed to do studies with more epidemiologic power and same methodology of study to be more comparable.

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.

Retinal displacement following pars plana vitrectomy with silicone oil tamponade for rhegmatogenous retinal detachment.

PURPOSE: To evaluate the frequency of retinal displacement after pars plana vitrectomy (PPV) using silicone oil tamponade in patients with rhegmatogenous retinal detachment (RRD). METHODS: Patients with fresh RRD were enrolled in this prospective interventional case series. A standard 3-port PPV with silicone oil tamponade was performed in all cases. A complete ocular examination, optical coherence tomography and fundus autofluorescence (FAF) imaging were performed at 1 and 3 months follow-up. Orthoptic examinations including synoptophore and light on-off tests were also performed at 3 months. RESULTS: Twenty-three eyes from 23 patients with mean age of 56.6 ± 11 (range: 38-82) years were included. All patients were pseudophakic. Downward retinal displacement was found in 2 eyes (8.7%) showing hyperautofluorescent lines parallel to retinal vessels in FAF image. The patients with retinal displacement did not complain of metamorphopsia and did not show abnormality in orthoptic tests. CONCLUSION: Unintentional retinal shift following PPV with silicone oil tamponade for RRD is uncommon and might have little clinical significance.

Ocular flare-up in patients with systemic lupus erythematosus following discontinuation of hydroxychloroquine.

In this report, we describe two patients with systemic lupus erythematosus (SLE) who manifested with posterior segment flare-up approximately three months after cessation of hydroxychloroquine (HCQ). They were stable systemically with no history of hypertension or nephropathy at the time of referral. Our first patient presented with bilateral retinal vein occlusion, while evidence of choroidal involvement such as vascular leakage and wedge-shaped filling delay was present in indocyanine green angiography of both patients. HCQ is well known to have a role in the treatment of SLE for its immunomodulatory and antithrombotic effects. Although reports of systemic flare-up of SLE following HCQ cessation exist in the literature, this is the first report of ocular flare-up in such settings.

Optical coherence tomography angiography changes in macula-off rhegmatogenous retinal detachments repaired with silicone oil.

PURPOSE: To evaluate the changes on optical coherence tomography angiography (OCTA) in macula-off rhegmatogenous retinal detachments (RRD) treated with pars plana vitrectomy (PPV) and silicone oil (SO) 5000-cSt tamponade. MATERIALS AND METHOD: Forty-five eyes with macula-off RRD treated with PPV and SO tamponade were enrolled with the fellow eye being used as a control. OCT-A was obtained using the RTVue XR 100 Avanti (Optovue, Inc., Fremont, CA, USA) at the 1-week, 1-month, and 3-month postoperative visit. Retinal vascular density, choroidal flow area, retinal thickness, and foveal avascular zone area were evaluated at each follow-up visit. Changes in these parameters in the postoperative eye were tracked at each follow-up visit as were the relative differences between the postoperative eye and the contralateral eye. RESULTS: Vascular density of parafoveal superficial capillary plexus and total retina demonstrated significant decrease in the postoperative silicone-filled eye when compared to the fellow eye (P < 0.0001). Although there was some improvement in these values at subsequent follow-ups, they remained less than the fellow eye. Foveal (P = 0.002) and parafoveal (P < 0.0001) thickness were less than the fellow eye. Choroidal flow area did not show a significant change in operated eye compared with the fellow eye. CONCLUSION: Eyes with macula-off RRD repaired with PPV and SO, at 3-month follow-up, demonstrated less retinal vascular density at parafoveal area as well as lower retinal thickness at fovea when compared to the healthy fellow eyes.

An investigation on optic nerve head involvement in Fuchs uveitis syndrome using optical coherence tomography and fluorescein angiography.

PURPOSE: To investigate optic nerve head involvement in patients with Fuchs uveitis syndrome (FUS). METHODS: Optic nerve head of 43 FUS eyes without clinical optic disc edema and 37 unaffected fellow eyes were evaluated using optical coherence tomography (OCT) of peripapillary retina and retinal nerve fiber layer (RNFL) and fundus fluorescein angiography. RESULTS: Seventy-one percent of FUS eyes showed optic nerve head hyperfluorescence. The mean average RNFL thickness in FUS eyes was 115.0 ± 11.9 µm, which was thicker than unaffected eyes (103.0 ± 10.7 µm, p < 0.001). Mean average of peripapillary retinal thicknesses in FUS eyes was also greater than unaffected eyes (p < 0.001). In addition, RNFL and peripapillary retinal thicknesses in FUS eyes without optic nerve hyperfluorescence were thicker than unaffected eyes (all p = < 0.001). CONCLUSIONS: OCT demonstrates peripapillary total retinal and nerve fiber layer thickening in FUS eyes without clinical swelling of optic disc that is not always associated with optic nerve head leakage.

Defective initiation of glycosaminoglycan synthesis due to B3GALT6 mutations causes a pleiotropic Ehlers-Danlos-syndrome-like connective tissue disorder.

Proteoglycans are important components of cell plasma membranes and extracellular matrices of connective tissues. They consist of glycosaminoglycan chains attached to a core protein via a tetrasaccharide linkage, whereby the addition of the third residue is catalyzed by galactosyltransferase II (ß3GalT6), encoded by B3GALT6. Homozygosity mapping and candidate gene sequence analysis in three independent families, presenting a severe autosomal-recessive connective tissue disorder characterized by skin fragility, delayed wound healing, joint hyperlaxity and contractures, muscle hypotonia, intellectual disability, and a spondyloepimetaphyseal dysplasia with bone fragility and severe kyphoscoliosis, identified biallelic B3GALT6 mutations, including homozygous missense mutations in family 1 (c.619G>C [p.Asp207His]) and family 3 (c.649G>A [p.Gly217Ser]) and compound heterozygous mutations in family 2 (c.323_344del [p.Ala108Glyfs(∗)163], c.619G>C [p.Asp207His]). The phenotype overlaps with several recessive Ehlers-Danlos variants and spondyloepimetaphyseal dysplasia with joint hyperlaxity. Affected individuals' fibroblasts exhibited a large decrease in ability to prime glycosaminoglycan synthesis together with impaired glycanation of the small chondroitin/dermatan sulfate proteoglycan decorin, confirming ß3GalT6 loss of function. Dermal electron microcopy disclosed abnormalities in collagen fibril organization, in line with the important regulatory role of decorin in this process. A strong reduction in heparan sulfate level was also observed, indicating that ß3GalT6 deficiency alters synthesis of both main types of glycosaminoglycans. In vitro wound healing assay revealed a significant delay in fibroblasts from two index individuals, pointing to a role for glycosaminoglycan defect in impaired wound repair in vivo. Our study emphasizes a crucial role for ß3GalT6 in multiple major developmental and pathophysiological processes.

Ocular morbidities of juvenile idiopathic arthritis-associated uveitis in adulthood: results from a tertiary center study.

PURPOSE: To describe the clinical and visual outcomes of juvenile idiopathic arthritis (JIA)-associated uveitis in adults and to examine risk factors for ongoing inflammation in adulthood. METHODS: Medical records were reviewed for patients with JIA-associated uveitis who were >16 years old at the final visit (the last visit prior to data collection). RESULTS: In total, 135 eyes of 77 patients (70 female, 7 male) were included. The mean age of patients at the final visit was 29.72 ± 11.27 years. The number of eyes with visual acuity of ≤20/50 and ≤20/200 at the final visit was 37 (28 %) and 20 (15 %), respectively; at least one ocular complication was present in 72 % of eyes. Band keratopathy was the most frequent complication (42 %), followed by cataract (25 %), posterior synechiae (22 %), maculopathy (22 %), ocular hypertension (13 %), and hypotony (5 %). At the final visit, patients who were >16 years of age at presentation to the Massachusetts Eye Research and Surgery Institution had more ocular complications and a greater degree of vision loss than patients who were ≤16 years of age. Ongoing inflammation at the final visit was noted in 40 patients (52 %). The presence of posterior synechiae, hypotony, cataract at presentation, and a history of cataract surgery prior to presentation were predictive of ongoing inflammation in adulthood in univariate analysis. The presence of hypotony and posterior synechiae at the initial visit were predictive factors in multivariate analysis. CONCLUSIONS: JIA-associated uveitis may be associated with ongoing inflammation, ocular complications, and severe visual impairment in adulthood. The presence of posterior synechiae and hypotony at the initial visit is predictive of ongoing inflammation.

Comparison of Refractive Error Changes in Retinopathy of Prematurity Patients Treated with Diode and Red Lasers.

AIM: To compare refractive error changes in retinopathy of prematurity (ROP) patients treated with diode and red lasers. METHODS: A randomized double-masked clinical trial was performed, and infants with threshold or prethreshold type 1 ROP were assigned to red or diode laser groups. Gestational age, birth weight, pretreatment cycloplegic refraction, time of treatment, disease stage, zone and disease severity were recorded. Patients received either red or diode laser treatment and were regularly followed up for retina assessment and refraction. The information at month 12 of corrected age was considered for comparison. RESULTS: One hundred and fifty eyes of 75 infants were enrolled in the study. Seventy-four eyes received diode and 76 red laser therapy. The mean gestational age and birth weight of the infants were 28.6 ± 3.2 weeks and 1,441 ± 491 g, respectively. The mean baseline refractive error was +2.3 ± 1.7 dpt. Posttreatment refraction showed a significant myopic shift (mean 2.6 ± 2.0 dpt) with significant difference between the two groups (p < 0.001). There was a greater myopic shift among children with zone I and diode laser treatment (mean 6.00 dpt) and a lesser shift among children with zone II and red laser treatment (mean 1.12 dpt). The linear regression model, using the generalized estimating equation method, showed that the type of laser used has a significant effect on myopic shift even after adjustment for other variables. CONCLUSION: Myopic shift in laser-treated ROP patients is related to the type of laser used and the involved zone. Red laser seems to cause less myopic shift than diode laser, and those with zone I involvement have a greater myopic shift than those with ROP in zone II.

Retinal detachment, vitreous hemorrhage, and foveal hypoplasia associated with 3q27.1q27.2 microdeletion: a case report.

Terminal deletions of chromosome 3q are associated with a heterogenous clinical phenotype, which includes growth restriction, developmental delay, and intellectual disability. However, little has been published on the ophthalmic impacts of chromosome 3q deletions. We report a 9-year-old boy with a 1.4 megabase deletion of 3q27.1q27.2 whose ocular morbidities included retinal detachment in one eye, vitreous hemorrhage in the other eye, and foveal hypoplasia in both eyes that required acute care and continuous ophthalmologic follow-up.

Bilateral helicoid peri-papillary sub-retinal fibrosis due to a biallelic NR2E3 mutation: Describing variable expressivity of a mutation.

BACKGROUND: To describe different clinical presentations of a same NR2E3 recessive mutation in two families and within one family. DESIGN: Interventional family study. RESULTS: Our first case was a one-year-old male child with high hyperopia and refractive accommodative esotropia. In retinal examination, peri-papillary sub-retinal fibrosis with a helicoid configuration was observed in both eyes. The parents and the only sibling had no pathologic findings in the eyes. The child showed to have severely reduced responses in both photopic and scotopic electroretinogram components. In the genetic investigation, a homozygous autosomal recessive mutation in the NR2E3 gene (IVS1-2A > C) was discovered in the affected child, while the other family members were heterozygous for this mutation. We followed up with the patient for 3 years and no new lesion developed during this period. The second case was a 13-year-old male child referred to the retina clinic for decreased vision in the right eye. In retina examination, there were nummular pigmentary changes at the level of retinal pigment epithelium and along the vascular arcades with foveo-schitic changes in both eyes. A choroidal neovascularization (CNV) was noticed in the macula of his right eye. The genetic evaluation proved the same mutation in the NR2E3 gene as in the first case. Family history was remarkable for an uncle, an aunt, and two cousins with night blindness. CONCLUSION: Same NR2E3 gene mutation can cause heterogeneous clinical manifestations such as slight retinal changes in the absence of any visual symptoms to high hyperopia associated with helicoid peri-papillary sub-retinal fibrosis.

A case report of pediatric-onset MS associated uveitis.

BACKGROUND: To report a case of Pediatric-onset MS associated uveitis managed with local and systemic medications. CASE PRESENTATION: An 11-year-old boy who was diagnosed with Pediatric-onset MS (POMS) with the first presentation of left optic neuritis in another center, was referred to our clinic with the complaint of non-improved vision in the left eye despite receiving IV 5gr methylprednisolone. After the ophthalmologic examinations, the patient was diagnosed as bilateral POMS-associated intermediate uveitis, and local treatment with corticosteroid was administered to both eyes. He was continued on systemic therapy such as Rituximab and five sessions of plasmapheresis. After four months, the patient's vision improved from FC at 50cm to 9/10 in the left eye. The intensity of intraocular inflammation decreased in both eyes. In fluorescein angiography findings, the optic disc, as well as vascular leakage, subsided bilaterally. CONCLUSION: Despite its rarity, POMS-associated uveitis presents a considerable challenge that necessitates the collaborative efforts of neurologists and ophthalmologists to achieve the most effective treatment outcomes.

Automated diagnosis of plus disease in retinopathy of prematurity using quantification of vessels characteristics.

The condition known as Plus disease is distinguished by atypical alterations in the retinal vasculature of neonates born prematurely. It has been demonstrated that the diagnosis of Plus disease is subjective and qualitative in nature. The utilization of quantitative methods and computer-based image analysis to enhance the objectivity of Plus disease diagnosis has been extensively established in the literature. This study presents the development of a computer-based image analysis method aimed at automatically distinguishing Plus images from non-Plus images. The proposed methodology conducts a quantitative analysis of the vascular characteristics linked to Plus disease, thereby aiding physicians in making informed judgments. A collection of 76 posterior retinal images from a diverse group of infants who underwent screening for Retinopathy of Prematurity (ROP) was obtained. A reference standard diagnosis was established as the majority of the labeling performed by three experts in ROP during two separate sessions. The process of segmenting retinal vessels was carried out using a semi-automatic methodology. Computer algorithms were developed to compute the tortuosity, dilation, and density of vessels in various retinal regions as potential discriminative characteristics. A classifier was provided with a set of selected features in order to distinguish between Plus images and non-Plus images. This study included 76 infants (49 [64.5%] boys) with mean birth weight of 1305 ± 427 g and mean gestational age of 29.3 ± 3 weeks. The average level of agreement among experts for the diagnosis of plus disease was found to be 79% with a standard deviation of 5.3%. In terms of intra-expert agreement, the average was 85% with a standard deviation of 3%. Furthermore, the average tortuosity of the five most tortuous vessels was significantly higher in Plus images compared to non-Plus images (p ≤ 0.0001). The curvature values based on points were found to be significantly higher in Plus images compared to non-Plus images (p ≤ 0.0001). The maximum diameter of vessels within a region extending 5-disc diameters away from the border of the optic disc (referred to as 5DD) exhibited a statistically significant increase in Plus images compared to non-Plus images (p ≤ 0.0001). The density of vessels in Plus images was found to be significantly higher compared to non-Plus images (p ≤ 0.0001). The classifier's accuracy in distinguishing between Plus and non-Plus images, as determined through tenfold cross-validation, was found to be 0.86 ± 0.01. This accuracy was observed to be higher than the diagnostic accuracy of one out of three experts when compared to the reference standard. The implemented algorithm in the current study demonstrated a commendable level of accuracy in detecting Plus disease in cases of retinopathy of prematurity, exhibiting comparable performance to that of expert diagnoses. By engaging in an objective analysis of the characteristics of vessels, there exists the possibility of conducting a quantitative assessment of the disease progression's features. The utilization of this automated system has the potential to enhance physicians' ability to diagnose Plus disease, thereby offering valuable contributions to the management of ROP through the integration of traditional ophthalmoscopy and image-based telemedicine methodologies.

Hemicentral retinal vein occlusion in a patient with a history of coronavirus disease 2019 infection: a case report and review of the literature.

BACKGROUND: Considering the various manifestations of coronavirus disease 2019 and its imperative importance in terms of the right clinical approach and early management, we sought to present a hemicentral retinal vein occlusion case, with a history of heterozygosity of methylenetetrahydrofolate reductase (MTHFR) genes and potential for clotting complications as a late manifestation of coronavirus disease 2019, and provide a brief review of reported retinal vein occlusion cases in patients with coronavirus disease 2019. CASE PRESENTATION: A 35-year-old Iranian patient presented with a visual impairment in the left eye 4 months after recovering from coronavirus disease 2019. He reported a mild blurring of vision in the same eye a few days after admission due to coronavirus disease 2019. The ophthalmic evaluation was compatible with hemicentral retinal vein occlusion. Systemic and laboratory workups were negative except for borderline protein C activity, homocysteine levels, and heterozygosity of MTHFR genes. The patient was scheduled to receive three monthly intravitreal antivascular endothelial growth factor injections. CONCLUSION: We present a case of inferior hemicentral retinal vein occlusion case with an MTHFR mutation with sequential loss of vision 4 months after coronavirus disease 2019 to make clinicians aware of the possibility of late ocular coronavirus disease 2019 manifestations.

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.