PURPOSE: To investigate the recent 8-year epidemiology of retinopathy of prematurity (ROP) and treatment modalities in Taiwan. MATERIALS AND METHODS:A retrospective study was conducted from 2016 to 2023, using data from Chang Gung Memorial Hospital, Linkou, Taiwan, and enrolling 2078 premature babies who were screened for ROP. The incidence of ROP, type 1 ROP, and initial treatment were analyzed. RESULTS:ROP developed in 671 of the 2078 infants (29.7%), and type 1 ROP was present in 195 infants (9.4%). A declining trend was observed in the number of ROP screenings among premature infants (P = 0.02). The proportion of type 1 ROP decreased significantly from 12.13% in 2016 to 5.0% in 2023 (P < 0.01). Antivascular endothelial growth factor (VEGF) was chosen in 97% and 93.2% of the initial and overall treatments, respectively, with laser mainly used as a secondary treatment. Bevacizumab was the most frequently selected option among the three available anti-VEGF drugs. CONCLUSION: The incidence of ROP between 2016 and 2023 showed no significant change. The proportion of type 1 ROP decreased during this period. Anti-VEGF was chosen as the initial treatment, and bevacizumab was the most frequently used agent.

PURPOSE:To investigate regional differences in the epidemiology and treatment of retinopathy of prematurity (ROP) from 2016 to 2023. STUDY DESIGN:Retrospective multicenter cohort study METHODS: Premature infants screened for ROP at a single tertiary referral center in each of five countries/regions (Taiwan, Hong Kong, Singapore, India, and Portugal) during the study period. Demographic characteristics, incidences of ROP and type 1 ROP, and treatment modalities were analyzed. Screening criteria followed local protocols. Logistic regression was used to assess trends, and intergroup comparisons were performed using Kruskal-Wallis and chi-square tests. RESULTS:A total of 15,031 premature infants were enrolled. Demographics varied significantly (p <0.001); India had the highest gestational age and birth weight, and the lowest proportion of very low birth weight and extremely low birth weight infants with type 1 ROP (p <0.001). Hong Kong had the lowest ROP incidence, while Singapore showed a significant increase over time (p = 0.003). Type 1 ROP rates were higher in Taiwan and India than in Hong Kong and Singapore, with a significant decline observed only in Taiwan (p = 0.005). Anti-Vascular Endothelial Growth Factor (Anti-VEGF) injections were increasingly preferred as initial treatment, with bevacizumab being the most frequently used (87.3%). CONCLUSION:From 2016 to 2023, ROP incidence and treatment showed significant regional differences. ROP increased in Singapore, while type 1 ROP decreased significantly in Taiwan. Although anti-VEGF therapy has become more common, laser treatment remains dominant in Hong Kong.

To investigate the molecular cause of choroideremia in two unrelated patients with no detectable mutations in the CHM gene. Two unrelated patients were examined by an ophthalmologist to obtain a clinical diagnosis. Patient and control cells were cultured and used as a source of DNA, RNA, and protein for analysis. Exonic regions of CHM were Sanger sequenced and copy number analysis was performed by multiplex ligation-dependent probe amplification. mRNA transcripts were analyzed by Sanger sequencing from synthesized cDNA. Protein expression was probed with western blot analysis. Suspecting an inversion, PCR in one case and inverse PCR in the second case were employed to locate the precise DNA breakpoints. Patient 1 and 2 were clinically diagnosed with choroideremia by experienced ophthalmologists. In both cases, sequencing of the promoter and coding regions of the CHM gene revealed no mutation and copy number analysis of the gene did not detect the presence of any large deletions or duplications. RNA obtained from the patient cells showed only a partial transcript in patient 1, and an abnormal CHM splice isoform in patient 2. The results from RNA and DNA analyses suggested that both patients' genomic DNA might contain an inversion mutation. In patient 1, a long-range PCR product amplified over two breakpoints confirmed an inversion event. This 6 kb inversion spanned from the 5'UTR to the first intron (NM_000390.4(CHM): c.[-836_-826del; 49 + 5526_49 + 5856del; -825_49 + 5525inv; insCGTCT].). In patient 2, inverse PCR revealed a different novel inversion of approximately 85 kb, spanning from intron 2 to intron 8 (NM_000390.4(CHM):c.116 + 6659_1166 + 20670inv). To detect these two inversions in future choroideremia samples, multiplex PCR assays were developed that produce distinct banding patterns that are diagnostic for these two mutations. We have identified inversion mutations in the CHM gene resulting in choroideremia. Though uncommon, inversions should be investigated as a possible cause of the disease in CHM patients, especially for those in whom no point mutations or copy number variants are found.

BACKGROUND:To evaluate ocular blood flow in school-aged children born prematurely, with or without retinopathy of prematurity (ROP), using laser speckle flowgraphy (LSFG), and to determine factors associated with LSFG-derived parameters. METHODS:This cross-sectional observational study included 123 school-aged preterm children: 54 without ROP, 20 with untreated type 2/mild ROP, and 49 with treated type 1 ROP. All participants underwent ophthalmic examinations and optic nerve head (ONH) perfusion assessments using LSFG. Mean blur rate indices of the entire ONH (MA), vessel area (MV), and tissue area (MT) of the right eye were analysed. Multivariable generalised linear models were used to identify variables associated with LSFG parameters, and Pearson's correlation was used to examine the association between axial length and MT. RESULTS:Children with type 1 ROP had lower MA, MV, and MT than those with type 2/mild ROP, whereas MV was the highest in the type 2/mild ROP group. Type 1 ROP was independently associated with reduced MA and MV in the full cohort. Among children with ROP, anti-vascular endothelial growth factor (VEGF) treatment was associated with lower MA, MV, and MT. Longer axial length correlated with reduced MT in both the full cohort (r = -0.30, p < 0.01) and the ROP subgroup (r = -0.35, p < 0.01). CONCLUSIONS:Type 1 ROP was associated with reduced ocular blood flow in school-aged children born preterm. Among eyes with ROP, a history of anti-VEGF treatment was associated with lower MA, MV, and MT, although this may reflect disease severity.

Autosomal recessive bestrophinopathy (ARB) typically results from biallelic BEST1 coding variants; however, the role of non-coding variants remains under-investigated. We report dizygotic twins with classic ARB who each initially appeared to carry only one frameshift mutation, later found to harbor a second deep intronic variant in trans. Complete ophthalmologic examination, diagnostic imaging, and electrophysiological study were performed. Genetic analysis included whole-exome sequencing followed by targeted Sanger sequencing of intronic regions, confirming BEST1 variants in five family members. Ten-year-old dizygotic twins presented with bilateral reduced visual acuity, hyperopia in at least one eye of each twin, multifocal yellow-white flecks, subretinal hyperreflective material with interlaminar splitting, and mild subretinal/intraretinal fluid. Electro-oculography revealed severely reduced Arden ratios, while full-field electroretinogram revealed subnormal rod and cone responses. Genetic testing identified in trans compound heterozygous BEST1 variants, a maternally inherited frameshift c.353_362dup and a paternally inherited deep intronic variant c.867+97G>A. Asymptomatic parents were heterozygous carriers. This is the first report of dizygotic twins with ARB carrying compound heterozygous BEST1 mutations consisting of a frameshift and the deep intronic variant c.867+97G>A inherited in trans.

To evaluate visual and refractive outcomes in school-aged patients with a history of prematurity and retinopathy of prematurity (ROP) with or without treatment. This is a retrospective cross-sectional study. Participants were categorized into five groups: full-term, preterm without ROP, ROP without treatment, intravitreal injection of anti-vascular endothelial growth factor (IVI)-treated ROP, and laser indirect ophthalmoscopy (LIO)-treated ROP. Patients underwent comprehensive ophthalmic examinations, including cycloplegic refraction and optical biometry. Comparisons were stratified into two age cohorts: 5 ≤ AGE < 10 and 10 ≤ AGE ≤ 13. Refractive errors, axial length (AL), anterior chamber depth (ACD), corneal parameters, and lens thickness were measured and compared between the groups. A total of 310 patients were enrolled in the study. Significant intergroup differences in AL, ACD, white-to-white distance, and best-corrected visual acuity (BCVA) were observed across both age cohorts (all p < 0.05). In the older age cohort, post-hoc analysis revealed that LIO-treated eyes had significantly shorter AL (22.73 ± 1.51 mm vs. 24.39 ± 0.89 mm, p = 0.0057), shallower ACD (3.31 ± 0.46 mm vs. 3.78 ± 0.22 mm), smaller corneal diameter (11.53 ± 0.35 mm vs. 12.29 ± 0.42 mm, p = 0.0018), and steeper corneal curvature (46.23 ± 1.53 D vs. 42.95 ± 1.37 D, p = 0.0002) compared with full-term controls. When directly compared with IVI-treated eyes in the older cohort, LIO-treated eyes had significantly thinner corneas (p = 0.04) and steeper corneal curvature (p = 0.005). IVI-treated eyes exhibited biometric and refractive profiles similar to those of untreated ROP. ROP and its treatment have long-term effects on ocular development and refraction. Laser-treated patients exhibited significantly higher myopia and astigmatism, shorter axial length, shallower anterior chambers, and smaller corneal diameters, particularly in older age groups. In contrast, IVI-treated eyes had a biometry closer to that of untreated ROP.

NR2E3 is a nuclear orphan receptor essential for photoreceptor development. Variants in the NR2E3 gene are associated with autosomal recessive retinitis pigmentosa 37 (RP37) and enhanced S-cone syndrome (ESCS). We report a novel NR2E3 variant in a family with RP37, aiming to clarify pathogenicity through clinical and genetic evaluation. The proband, a 26-year-old woman, experienced childhood-onset nyctalopia and progressive vision loss. Fundus exam revealed mid-peripheral pigment clumps and parafoveal depigmentation. Fundus autofluorescence showed widespread hypo-autofluorescent lesions; spectral-domain OCT identified outer nuclear layer thinning and ellipsoid zone loss. Full-field electroretinography confirmed severely diminished scotopic and photopic responses. Her 23-year-old sister had milder pigmentary changes and cystoid macular edema, while their 20-year-old brother's phenotype was less pronounced. All three siblings were homozygous for a novel missense variant in NR2E3 (NM_014249.4:c.352 G > C; p.Val118Leu), located within the DNA-binding domain. Both parents were heterozygous carriers. A previously reported variant affecting the same codon but resulting in a different amino acid change, along with its elevated allele frequency in East Asian populations, suggests a founder effect and supports its pathogenic potential. This report supports reclassifying NR2E3 c.352 G > C (NM_014249.4) as likely pathogenic. A comprehensive genotype-phenotype analysis remains essential for advancing our understanding of NR2E3-associated retinal dystrophies.

Outer retinal tubulation (ORT) is a distinct structural manifestation of chronic photoreceptor degeneration, observed across a broad spectrum of retinal diseases. Initially described histologically as rosette-like formations, ORT has gained clinical relevance with the advent of high-resolution imaging modalities such as spectral-domain optical coherence tomography (SD-OCT) and adaptive optics scanning laser ophthalmoscopy (AO-SLO), which enable in vivo visualization of its tubular architecture. ORT arises from sustained photoreceptor and retinal pigment epithelium (RPE) injury, leading to the reorganization of surviving cones ensheathed by gliotic Müller cell processes. This review integrates historical, histological, and imaging data to elucidate ORT’s cellular composition, formation mechanisms, and disease-specific patterns. We introduce a novel etiological classification of ORT, categorized as degenerative, fibrotic, or edematous ORT according to predominant pathogenic drivers, to facilitate cross-disease comparison and prognostic stratification. Clinically, ORT serves as a non-exudative biomarker of chronic retinal injury, aiding differential diagnosis and informing treatment strategies. In age-related macular degeneration, ORT is associated with subretinal fibrosis and poor visual outcomes; in geographic atrophy, it may signal slower lesion progression. In inherited retinal dystrophies, ORT reflects genotype-specific vulnerabilities and residual photoreceptor survival, with implications for therapeutic targeting. As imaging technologies advance, ORT offers promise as a structural marker of disease chronicity, photoreceptor resilience, and Müller cell plasticity, enhancing diagnostic precision and supporting its role as a meaningful endpoint in clinical trials.

Systemic corticosteroids and immunosuppressants remain the standard first-line therapy for non-anterior, non-infectious uveitis (NIU), but prolonged use carries significant systemic and ocular adverse effects. Several intraocular agents have recently emerged as effective alternative or adjunctive options. Our meta-analysis included 9 randomized controlled trials and 1 retrospective case series, investigating the efficacy and safety profiles of intravitreal fluocinolone acetonide implant (FAi), intravitreal dexamethasone implant, intravitreal or suprachoroidal triamcinolone acetonide (SCTA), intravitreal methotrexate, intravitreal ranibizumab, and standard of care (SOC) for NIU. Our results demonstrated that all the studied intraocular agents excluding ranibizumab demonstrated a better best-corrected visual acuity gain compared to SOC at 6 months. The 4 mg SCTA demonstrated the greatest central macular thickness reduction surpassing other intraocular steroid therapies and SOC at 6 months for uveitic macular edema. With regards to side effects, 0.59 mg FAi was associated with a higher risk of 2-year and 3-year intraocular pressure elevation ≥ 10 mmHg when compared to SOC. Understanding the advantages and limitations of intraocular therapies is essential for initiating personalized treatment strategies in NIU.

PURPOSE:The purpose of the study was to evaluate factors influencing outpatient follow-up adherence among patients receiving ophthalmology consultations in the emergency department (ED). MATERIALS AND METHODS:This retrospective cohort study collected data from the Chang Gung Research Database. Patients who received ophthalmology consultations at the ED of Chang Gung Memorial Hospital Linkou Medical Center from January 1, 2010, to December 31, 2019, were included. Patients were divided into two groups based on whether they completed outpatient follow-up within 28 days, a timeframe consistent with our hospital's scheduling policy. Demographics, ED visit timing, triage categories, ophthalmic diagnoses, prior visits, and ED stay durations were analyzed using logistic regression. RESULTS:A total of 42,530 patients were included (mean age 38.6 ± 20.2 years; 59.2% male), with 38.4% adhering to follow-up and 61.6% not. Nonadherence was associated with younger age (odds ratio [OR]: 0.92; 95% confidence interval [CI]: 0.92-0.93), evening (OR: 1.28; 95% CI: 1.22-1.34) or midnight (OR: 1.94; 95% CI: 1.83-2.06) ED visits, not likely emergent diagnoses (OR: 2.09; 95% CI: 1.96-2.22), and shorter ED stays (<1 h: OR: 3.73; 95% CI: 3.46-4.03). Patients with prior ophthalmology outpatient visits (OR: 0.48; 95% CI: 0.46-0.52) and longer ED stays (more than 3 h) demonstrated better adherence. Over 10 years, emergent diagnoses increased from 51.1% to 69.5%, while non-emergent diagnoses declined from 23.1% to 13.2%. CONCLUSION:Adherence to outpatient follow-up after ophthalmic ED visits was low. Younger age, evening or midnight visits, non-emergent diagnoses, and short ED stays predicted non-adherence, whereas prior outpatient visits and longer ED stays improved adherence.

PURPOSE: The study compared the clinical features and ocular examination results between patients with Alstr & ouml;m syndrome (AS) and those with achromatopsia (ACHM). MATERIALS AND METHODS: Four patients with AS and seven patients with ACHM were analyzed using whole-exome sequencing (and subsequent Sanger sequencing) to identify ALMS1 and ACHM-related disease-causing variants. Genetic profiles and clinical characteristics were assessed, with color fundus imaging, fundus autofluorescence, spectral domain optical coherence tomography (SD-OCT), and electroretinography results compared between the two groups. RESULTS: Fundus imaging revealed progressive retinal changes and extra-macular degeneration in patients with AS but stationary macular alterations in those with ACHM. SD-OCT showed that three patients with AS had outer nuclear layer (ONL) thinning and ellipsoid zone loss beyond the fovea, whereas one patient had severe retinal changes. By contrast, all patients with ACHM exhibited subfoveal ONL thinning. Full-field electroretinography revealed diminished rod and cone responses in three patients with AS but rod function preservation in all patients with ACHM. Furthermore, systemic involvement distinguished AS from ACHM. Notably, one patient with ACHM exhibited a digenic triallelic inheritance pattern. CONCLUSION: This study improves our understanding of the genetic and phenotypic differences between AS and ACHM, thereby increasing diagnostic precision.

Autosomal dominant optic atrophy (ADOA) is a hereditary optic neuropathy caused by OPA1 variants, leading to retinal ganglion cell (RGC) degeneration and vision loss. The mechanisms behind RGC vulnerability to mitochondrial dysfunction remain unclear. We developed a patient-specific Opa1V291D/+ knock-in mouse model to investigate mitochondrial dysfunction and retinal metabolism in ADOA. We observed that Opa1V291D/+ mice exhibited anatomical and functional RGC abnormalities recapitulating the ADOA phenotypes. Reduced optic atrophy 1 (OPA1) protein levels were noted in Opa1V291D/+ mice, accompanied by decreased protein stability. Moreover, mitochondrial function was compromised, as indicated by reduced Complex I activity, increased oxidative stress, and diminished adenosine triphosphate production in the retinas of Opa1V291D/+ mice. Spatial metabolomics revealed energy deficits in the inner retina and heightened glycolysis in the outer retina. Immunostaining showed decreased expression of glycolytic proteins in the ganglion cell layer. Single-nucleus RNA sequencing disclosed significant down-regulation of energy-production genes in RGCs, while other retinal cell types remained unaffected. These findings emphasize the specific vulnerability of RGCs to bioenergetic crises, connecting disrupted energy homeostasis to their degeneration. By increasing the nicotinamide adenine dinucleotide (NAD+)/reduced form of NAD+ (NADH) redox ratio through the overexpression of mitochondrial-targeted Lactobacillus brevis NADH oxidase (MitoLbNOX) in RGCs, we demonstrated improved RGC function and survival through enhanced energy metabolism and reduced oxidative stress. These findings confirm that disrupted energy metabolism leads to RGC degeneration and emphasize the enhancement of the NAD+/NADH redox ratio as a promising treatment strategy to protect RGCs from degeneration in ADOA.

The current study explores the association between pigment epithelium-derived factor (PEDF) polymorphisms and risk, severity, susceptibility, and treatment response of retinopathy of prematurity (ROP). The study is designed in a prospective cohort manner, where all participating patients were recruited from two hospital branches. Three single nucleotide polymorphisms (SNPs) of PEDF with the highest allele frequency were selected. The genomic data were extracted from the patient's blood and amplified using polymerase chain reaction (PCR). A multivariate logistic regression model assessed the association between PEDF polymorphisms and ROP risk. Risk evaluation for each polymorphism was performed using an adjusted odds ratio (OR). 51 % of the 585 recruited patients developed ROP, subdivided into groups of type-2 or milder ROP and type-1 ROP. The results showed that patients with polymorphic genotype GA and the combination of genotypes GA and AA in the polymorphism of rs11658342 were associated with a higher risk of developing both type-2 or milder ROP (aOR = 1.757, p = 0.037; OR = 1.370, p = 0.013) and type-1 ROP (OR = 1.950, p = 0.013; OR = 1.358, p = 0.017). Patients with the polymorphic AA genotype in the polymorphism of rs12603825 had a higher risk of type-1 ROP (OR = 2.740, p = 0.029). The results indicate that patients with GA and AA genotypes in rs11658342 and rs12603825 of the PEDF polymorphism may serve as prognostic factors for ROP risks and severity.

Huang, Yi-Chen M.D; Wang, Nan-Kai M.D., Ph.D; Liu, Pei-Kang M.D., Ph.D Author Information

Purpose: To report a case of a 19-year-old male with Optic Atrophy-13 (OPA13) associated with a de novo heterozygous missense variant in the single-strand DNA-binding protein 1 (SSBP1) gene, characterized by a bilateral double C-shaped hyper-autofluorescent ring on fundus autofluorescence (FAF). Observations: A 19-year-old male exhibited poor visual acuity, pale optic discs, vessel attenuation, and peripheral pigmentary changes. FAF imaging revealed a bilateral double C-shaped hyper-autofluorescent ring, which was not frequently observed. Optical coherence tomography (OCT) showed retinal thinning and ellipsoid zone disruption, while electroretinography (ERG) indicated cone-rod dystrophy. Genetic testing identified a pathogenic SSBP1 missense variant, confirming the diagnosis of OPA13. Parental genetic analysis excluded the variant, establishing it as a de novo one. Conclusions and importance: This report highlights a novel retinal feature—a double C-shaped autofluorescent ring—associated with OPA13, potentially serving as a diagnostic marker for the disease. The findings emphasize the role of genetic testing in diagnosing OPA13 and distinguishing it from other retinal and optic neuropathies. Recognition of this feature could enhance early diagnosis and management strategies for patients with suspected OPA13.

Ocular blood flow imaging techniques have become indispensable in current clinical practice because retinal vascular disturbances have been implicated in the pathophysiology of numerous ocular diseases. In this review, we explore the applications of laser Doppler flowmetry, laser speckle flowgraphy (LSFG), and optical coherence tomography angiography (OCTA), focusing on LSFG and OCTA. Each modality is discussed in detail, including its principles, key parameters, advantages, limitations, and common artifacts. We further evaluated their roles in several ocular diseases, including age-related macular degeneration, polypoidal choroidal vasculopathy, diabetic retinopathy, retinal vein occlusion, retinal artery occlusion, pathologic myopia, glaucoma, non-arteritic anterior ischemic optic neuropathy, and retinopathy of prematurity. Finally, we discuss emerging advancements such as neonatal imaging devices, ultrawide-field OCTA, and artificial intelligence integration in vascular analysis.

PURPOSE:This study investigated the use of human amniotic membrane graft transplantation for treating recurrent large macular holes in highly myopic patients, particularly in cases resistant to standard surgical methods. METHODS:Seven eyes from six highly myopic patients with recurrent large macular holes (>400 µ m) underwent human amniotic membrane transplantation supported by perfluorocarbon liquid and ophthalmic viscoelastic devices. All patients had previously undergone pars plana vitrectomy with internal limiting membrane peeling. The human amniotic membrane graft, sized to cover the macular area, was carefully positioned with perfluorocarbon liquid and ophthalmic viscoelastic device assistance to enhance surgical control and prevent graft displacement. RESULTS:Complete macular hole closure was achieved in most cases. Best-corrected visual acuity was either preserved or improved, with no complications such as retinal detachment or graft displacement. The modified technique also reduced the need for prolonged prone positioning, minimizing postoperative discomfort for patients. CONCLUSION:Human amniotic membrane graft transplantation with perfluorocarbon liquid and ophthalmic viscoelastic device is a safe and effective method for managing large, recurrent macular holes in highly myopic eyes. This technique enhances graft handling, simplifies surgery, and achieves high closure rates with stable visual outcomes, offering a promising solution when conventional methods are inadequate.

Purpose:This study aimed to develop and evaluate a deep learning model for grading foveal hypoplasia using retinal fundus images. Methods:This retrospective study included patients with foveal developmental disorders, using color fundus images and optical coherence tomography scans taken between January 1, 2001, and August 31, 2021. In total, 605 retinal fundus images were obtained from 303 patients (male, 55.1%; female, 44.9%). After augmentation, the training, validation, and testing data sets comprised 1229, 527, and 179 images, respectively. A deep learning model was developed for binary classification (normal vs. abnormal foveal development) and six-grade classification of foveal hypoplasia. The outcome was compared with those by senior and junior clinicians. Results:Higher grade of foveal hypoplasia showed worse visual outcomes (P < 0.001). The binary classification achieved a best testing accuracy of 84.36% using the EfficientNet_b1 model, with 84.51% sensitivity and 84.26% specificity. The six-grade classification achieved a best testing accuracy of 78.21% with the model. The model achieved an area under the receiver operating characteristic curve (AUROC) of 0.9441 and an area under the precision-recall curve (AUPRC) of 0.9654 (both P < 0.0001) in the validation set and an AUROC of 0.8777 and an AUPRC of 0.8327 (both P < 0.0001) in the testing set. Compared to junior and senior clinicians, the EfficientNet_b1 model exhibited a superior performance in both binary and six-grade classification (both P < 0.00001). Conclusions:The deep learning model in this study proved more efficient and accurate than assessments by junior and senior clinicians for identifying foveal developmental diseases in retinal fundus images. With the aid of the model, we were able to accurately assess patients with foveal developmental disorders. Translational Relevance:This study strengthened the importance for a pediatric deep learning system to support clinical evaluation, particularly in cases reliant on retinal fundus images.

Diabetic retinopathy (DR) and diabetic macular edema (DME) are leading causes of vision loss globally. This is a comprehensive review focused on both medical and surgical management strategies for DR and DME. This review highlights the epidemiology of DR and DME, with a particular emphasis on the Asia-Pacific region, urban-rural disparities, ethnic variations, and grading methodologies. We examine various risk factors for DR, including glycemic control, hypertension, hyperlipidemia, obesity, chronic kidney disease, sex, myopia, pregnancy, and cataract surgery. Furthermore, we explore potential biomarkers in serum, proteomics, metabolomics, vitreous, microRNA, and genetics that may aid in the detection and management of DR. In addition to medical management, we review the evidence supporting systemic and ocular treatments for DR/DME, including anti-vascular endothelial growth factor (anti-VEGF) agents, anti-inflammatory agents, biosimilars, and integrin inhibitors. Despite advancements in treatment options such as pan-retinal photocoagulation and anti-VEGF agents, a subset of cases still progresses, necessitating vitrectomy. Challenging diabetic vitrectomies pose difficulties due to complex fibrovascular proliferations, incomplete posterior vitreous detachment, and fragile, ischemic retinas, making membrane dissection risky and potentially damaging to the retina. In this review, we address the question of challenging diabetic vitrectomies, providing insights and strategies to minimize complications. Additionally, we briefly explore newer modalities such as 3-dimensional vitrectomy and intra-operative optical coherence tomography as potential tools in diabetic vitrectomy. In conclusion, this review provides a comprehensive overview of both medical and surgical management options for DR and DME. It underscores the importance of a multidisciplinary approach, tailored to the needs of each patient, to optimize visual outcomes and improve the quality of life for those affected by these sight-threatening conditions.