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Open research questions in Retinal Diseases and Treatments

279 unresolved questions extracted from the limitations and future-work sections of 679 Retinal Diseases and Treatments papers in our library. Each links back to the study that raised it.

What the literature leaves open

  • Chronic hyperglycemia contributes to retinal microvascular damage through oxidative stress, inflammation, and endothelial dysfunction. The mechanism of the development of retinopathy is yet unknown. There is a need for early identification of risk factors for diabetic retinopathy.

    CORRELATION BETWEEN SERUM VITAMIN D LEVEL WITH DIABETIC RETINOPATHY: A OBSERVATIONAL PROSPECTIVE STUDY · 2026 · DOI

  • There is a lack of understanding of the relationship between serum vitamin D levels and diabetic retinopathy. Emerging evidence suggests that vitamin D deficiency may contribute to the development and progression of DR, but data remain limited and sometimes inconsistent.

    CORRELATION BETWEEN SERUM VITAMIN D LEVEL WITH DIABETIC RETINOPATHY: A OBSERVATIONAL PROSPECTIVE STUDY · 2026 · DOI

  • The lack of a significant link between visual acuity and certain optical coherence tomography measurements in prior research. The need for additional biomarkers to assess visual potential in patients with proliferative diabetic retinopathy. The limited understanding of the relationship between papillomacular bundle thickness and visual acuity.

    Papillomacular bundle thickness is associated with visual acuity in proliferative diabetic retinopathy · 2026 · DOI

  • The study had a small sample size. The study was retrospective and may be subject to biases. The follow-up period was limited to 12 months. The study did not include a control group that received no treatment. The study did not investigate the long-term effects of intravitreal ranibizumab.

    Intravitreal ranibizumab as an adjunct to conventional surgery for neovascular glaucoma: a retrospective observational study of efficacy and clinical characteristics of surgical failure cases · 2026 · DOI

  • Further study is needed to confirm the findings and fully understand the effects of intravitreal ranibizumab on neovascular glaucoma. Investigation of the long-term effects of intravitreal ranibizumab is necessary. A larger, prospective study would provide more robust results. Research into the optimal dosage and timing of intravitreal ranibizumab administration is needed.

    Intravitreal ranibizumab as an adjunct to conventional surgery for neovascular glaucoma: a retrospective observational study of efficacy and clinical characteristics of surgical failure cases · 2026 · DOI

  • The mechanisms underlying microglial PGRN downregulation are not well understood. The role of microglia-mediated neuroinflammation in retinal microvascular endothelial damage is not fully elucidated.

    Microglial PGRN downregulation contributes to phagocytosis-mediated retinal microvascular endothelial cell damage in early experimental diabetes · 2026 · DOI

  • The study identifies a gap in understanding the relationship between baseline wdHRM and short-term visual outcome in treatment-naive nAMD. The study highlights the need to consider both fibrosis-related and atrophy-related OCT biomarkers when interpreting short-term visual outcome.

    Macular neovascularisation subtype determines visual consequences of early fibro-atrophic remodelling in neovascular AMD: PRECISE study report 11 · 2026 · DOI

  • screening modality limited specificity in isolation and recommend multimodal confirmation for definite fibrosis in clinical studies [14]. Accordingly, in the present study, baseline HRM phenotypes were treated as a fibrosis-related biomarker rather than a definitive diagnosis of established fibrosis. for fibrosis, but emphasise its Increasing clinicoradiologic evidence indicates that fibrosis and atrophy are not mutually exclusive endpoints in treated nAMD but often co-localise, with residual HRM detectable within areas labelled as outer retinal or retinal pigment epithelium (RPE) atrophy. This fibro-atrophic continuum has recently been described as “atrosis” and may carry risks distinct from those of primary geographic atrophy in a non-neovascular context [19]. The heterogeneity in fibrosis propensity, atrophy and visual prognosis across MNV subtypes introduces further complexity. Observational and trial analyses converge on higher fibrosis risk in Type 2- or mixed lesions, lower rates in Type 3 MNV, and intermediate risk (and often sub‑RPE in phenotype) in Type 1 MNV [PCV]) (including polypoidal choroidal vasculopathy imply that unstratified [1, 20, 21]. These subtype patterns associations may be misleading and must be analysed with subtype‑specific context. These considerations leave several clinically relevant uncertain- ties at treatment initiation in nAMD. It remains unclear whether baseline wdHRM, used here as an OCT-defined biomarker of fibrotic remodelling, independently predicts short-term visual outcome after induction therapy, whether its functional con- sequences differ by MNV subtype, and how it relates at eye level to atrophy-related OCT biomarkers during early treatment. Using the PRECISE cohort, we addressed two related questions. First, we examined whether baseline wdHRM predicts BCVA after three monthly aflibercept for prespecified baseline and Visit 4 (V4) covariates. Second, we characterised the short-term evolution of HRM phenotypes and atrophy-related OCT eye-level their biomarkers by V4. injections, after adjustment association with METHODS

    Macular neovascularisation subtype determines visual consequences of early fibro-atrophic remodelling in neovascular AMD: PRECISE study report 11 · 2026 · DOI

  • The protective mechanisms of Scutellarin against retinal Müller cell injury in diabetic retinopathy remain unclear. The effects of Scutellarin on AQP4/Kir4.1 expression and TLR4/MyD88/NF-κB pathway in retinal Müller cells are unknown.

    Scutellarin attenuates high glucose-induced edema and inflammation in retinal Müller cells via AQP4/Kir4.1 restoration and TLR4/MyD88/NF-κB inhibition · 2026 · DOI

  • The diagnosis of atrial fibrillation relies on capturing sporadic heart rhythm abnormalities on an electrocardiogram. There is a need for earlier diagnosis of atrial fibrillation across broader communities.

    Atrial fibrillation and retinal imaging-based oculomics: A cross-sectional and longitudinal analysis of two large cohorts · 2026 · DOI

  • Further research is needed to understand the pathophysiological mechanisms underlying SRF and IRF accumulation in nAMD. Further research is needed to clarify the role of choroidal structural factors in SRF accumulation in nAMD.

    Association between choroidal structure and retinal fluid location in type 1 neovascular age-related macular degeneration · 2026 · DOI

  • Whether these structural char- acteristics influence anti-VEGF treatment response remains to be determined in prospective longitudinal studies. However, the mechanisms underlying these differ- ences were not fully understood. Some recent findings in other retinal diseases suggested that choroidal structural factors—such as venous congestion or vascular remodelling —might contribute to SRF accumulation, but their role in nAMD, particularly in type 1 choroidal neovascular mem- branes (CNVM), had not been clarified.

    Association between choroidal structure and retinal fluid location in type 1 neovascular age-related macular degeneration · 2026 · DOI

  • The study identifies the challenge of detecting diabetic retinopathy in its early stages, as it lacks typical clinical symptoms. The study also notes the challenge of establishing temporal or causal relationships between clinical factors and diabetic retinopathy due to its cross-sectional design.

    Factors associated with diabetic retinopathy: a cross-sectional study of 1477 patients across four cities in Anhui, China · 2026 · DOI

  • The study was cross-sectional and does not establish temporal or causal relationships, - Only 37 DR cases occurred in the HbA1c <6.5% stratum, making subgroup estimates underpowered, - Diabetes type was not entered into the primary model due to a substantial proportion of unknown values

    Factors associated with diabetic retinopathy: a cross-sectional study of 1477 patients across four cities in Anhui, China · 2026 · DOI

  • One challenge is the limited accessibility of prior biomarkers, which may be invasive or require specialized facilities and retinal specialists. Another challenge is the need for non-ocular biomarkers that can be used by non-ophthalmologists in community screenings. The paper also highlights the challenge of developing biomarkers with high accuracy and effectiveness in detecting DR.

    Non-ocular biomarkers for early diagnosis of diabetic retinopathy by non-invasive methods · 2025 · DOI

  • Further research on non-ocular biomarkers for early diagnosis of diabetic retinopathy is needed. Investigation of the correlation between AGE accumulation and the degree of DR is required. Development of more accurate and cost-effective non-invasive diagnostic biomarkers for DR.

    Non-ocular biomarkers for early diagnosis of diabetic retinopathy by non-invasive methods · 2025 · DOI

  • Further studies to validate the prognostic utility of retinal imaging in cardiac arrhythmias

    Atrial fibrillation and retinal imaging-based oculomics: A cross-sectional and longitudinal analysis of two large cohorts · 2026 · DOI

  • Whether graph-derived network architecture provides complementary information on severity remains unclear.

    Vascular geometry and network topology reveal vascular remodelling beyond density measures across Chew grades in macular telangiectasia type 2 · 2026 · DOI

  • The preferential detection of these structures in eyes with chronic CSC suggests disease-associated alterations in vitreous matrix organization and highlights a previously underexplored dimension of vitreous imaging.

    High-Resolution Optical Coherence Tomography Visualizes Posterior Vitreous Lamellar Architecture in Eyes With Chronic Central Serous Chorioretinopathy · 2026 · DOI

  • Abstract Background To date, the therapeutic potential of retinal organoid–derived exosomes (Exo-ROs) for retinal ganglion cell (RGC) preservation in chronic ocular hypertension (COH) has not been explored.

    Retinal organoid-derived exosomes enhance retinal ganglion cell survival in chronic ocular hypertension · 2026 · DOI

  • and its active metabolites in the prevention and treatment of retinal cell apoptosis, including essential aspects such as antioxidant activity, anti-inflammatory properties, autophagy regulation, and mitochondrial function preservation, is essential to establish a comprehensive and solid theoretical basis for further investigation of the medicinal value of L.

    Lycium barbarum L.: a potential botanical drug for preventing and treating retinal cell apoptosis · 2025 · DOI

  • Further validation in multicenter cohorts is warranted to confirm generalizability and enhance model robustness.

    A machine learning model for predicting anatomical response to Anti-VEGF therapy in diabetic macular edema · 2025 · DOI

  • While current research has predominantly focused on ocular imaging features and intraocular cytokine profiles, the role of systemic inflammation remains underexplored.

    Integration of peripheral blood-based systemic inflammatory indices and retinal imaging using interpretable machine learning for predicting anti-VEGF treatment response in macular edema secondary to retinal vein occlusion · 2025 · DOI

  • While current treatments, including anti-vascular endothelial growth factor (anti-VEGF) agents, corticosteroids, and laser photocoagulation, have shown clinical efficacy, they are largely limited to advanced stages of DR, require repeated invasive procedures, and do not adequately address early neurovascular and metabolic abnormalities.

    Resveratrol as a Novel Therapeutic Approach for Diabetic Retinopathy: Molecular Mechanisms, Clinical Potential, and Future Challenges · 2025 · DOI

  • However, 5-10% of the patients are poor responders with mechanisms remaining poorly understood.

    Aflibercept Resistance in Neovascular Age-Related Macular Degeneration 9210 · 2025 · DOI

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279 open questions have been extracted from the limitations and future-work passages of 679 Retinal Diseases and Treatments papers in our library. Each one below links back to the study that raised it, so you can read the original claim in context.

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