Recent Advance Questions - PG Ophthalmology (2025-2026)

RETINA & VITREOUS

1. Faricimab (Vabysmo) - mechanism and clinical evidence
   • What is the dual mechanism of faricimab as an anti-VEGF agent? How do the TENAYA and LUCERNE Phase 3 trials (2024 two-year data) justify its use in neovascular AMD with treat-and-extend dosing?
   • Compare faricimab vs. aflibercept head-to-head in terms of anatomic outcomes from TENAYA/LUCERNE.
2. Geographic Atrophy (GA) - first-ever approved treatments
   • What is pegcetacoplan (Syfovre) and avacincaptad pegol (Izervay)? What complement pathway do they target (C3 vs. C5)? What evidence supports their approval for GA secondary to AMD?
   • Discuss limitations of complement inhibitor therapy in GA: slow lesion growth reduction, injection burden, risk of conversion to wet AMD.
3. Gene Therapy for Inherited Retinal Diseases (IRDs)
   • Voretigene neparvovec (Luxturna) for RPE65-associated Leber Congenital Amaurosis - mechanism, vector (AAV2), surgical delivery (subretinal injection), patient selection criteria.
   • Botaretigene sparoparvovec (AAV5-hRKp.RPGR) Phase 1/2 trial outcomes for RPGR-associated X-linked Retinitis Pigmentosa.
   • What is cotoretigene toliparvovec? Summarize the XIRIUS Phase 2/3 trial in XLRP.
   • What are the challenges of gene therapy in RP: immune response, vector capacity, delivery method, durability of effect?
4. Optogenetic Therapy
   • Nanoscope's MCO-010 (voretigene in retinitis pigmentosa) - 5-year safety data 2025. What is the principle of optogenetics vs. gene replacement therapy?
5. Susvimo (Port Delivery System with ranibizumab)
   • FDA approved in May 2025 for diabetic retinopathy. Describe the port delivery system. What is its advantage over monthly intravitreal injections?
6. OCT-Angiography (OCTA) in Retinal Disease
   • What are the clinical applications of swept-source OCTA in proliferative diabetic retinopathy?
   • How does OCTA help in detecting subclinical CNV, superficial and deep capillary plexus changes, and foveal avascular zone changes in DME?
   • Limitations of OCTA vs. fluorescein angiography.
7. Ultra-Widefield Retinal Imaging
   • What is the role of ultra-widefield imaging (Optos, Clarus) in diabetic retinopathy staging?
   • How does peripheral retinal pathology detected on UWF imaging alter treatment decisions?
8. Fundus Autofluorescence (FAF)
   • What does hyperautofluorescence vs. hypoautofluorescence indicate in AMD?
   • Role of FAF in monitoring GA progression.
9. Polypoidal Choroidal Vasculopathy (PCV)
   • SALWEEN trial 2025: Faricimab (Vabysmo) for PCV in Asian patients - outcomes and injection interval extension.
   • How does PCV differ from typical neovascular AMD in Indian/Asian populations? How does ICGA guide treatment?
10. Retinopathy of Prematurity (ROP)
    • Bevacizumab vs. laser photocoagulation in zone I aggressive posterior ROP - current evidence.
    • What is "Plus disease"? Role of anti-VEGF in ROP - concerns about systemic VEGF suppression in premature infants.
    • RAINBOW trial and FIREFLEYE study outcomes.
11. Coats' Disease
    • Recent advances in management: intravitreal anti-VEGF combined with laser, role of anti-VEGF in advanced stages, staging system.

GLAUCOMA

1. Minimally Invasive Glaucoma Surgery (MIGS)
   • Classify MIGS procedures. Which are Schlemm's canal-based vs. suprachoroidal vs. subconjunctival?
   • Combined phacoemulsification + MIGS: Meta-analysis evidence (2025) for IOP reduction and medication reduction in open-angle glaucoma.
   • What are the outcomes of angle-based MIGS in normal tension glaucoma? (Cochrane/Meta-analysis 2024)
   • OMNI surgical system: mechanism and evidence for canaloplasty + trabeculotomy.
2. Novel Topical Agents for Glaucoma (2024-2025)
   • Netarsudil (Rho kinase inhibitor): mechanism, fixed combination with latanoprost (Rocklatan), clinical evidence.
   • Omidenepag isopropyl (VYZULTA-like prostaglandin EP2 receptor agonist): how does it differ from classical prostaglandins?
   • QLS-111 (Qlaris Bio): Phase 2 positive results 2025 - IOP reduction in OHT.
3. Sustained-Release Drug Delivery in Glaucoma
   • What are bimatoprost SR (Durysta), travoprost punctal plug, and bioerodible travoprost implants?
   • Discuss the rationale for sustained-release delivery to improve adherence.
4. Neuroprotection in Glaucoma
   • Current status of neuroprotective agents (brimonidine, memantine, citicoline). Are any proven in RCTs?
   • Optic nerve regeneration strategies: SOCS3/PTEN pathway manipulation, CNTF gene therapy.
5. AI in Glaucoma
   • How is AI/deep learning used for optic disc analysis, OCT RNFL interpretation, and visual field prediction?
   • What is the role of AI in glaucoma progression monitoring?

CORNEA & ANTERIOR SEGMENT

1. Corneal Collagen Cross-linking (CXL) in Keratoconus
   • Compare Dresden (standard), accelerated, and transepithelial (epithelium-on) CXL protocols. Which is most efficacious? (2026 Systematic Review)
   • What is the role of CXL in pediatric keratoconus?
   • Combination of CXL with topography-guided LASIK (TOPOLINK) - indications and evidence.
2. Bowman Layer Transplantation
   • What is the rationale for Bowman layer transplantation in advanced keratoconus? How does it flatten the cone without replacing the stroma?
3. DSAEK vs. DMEK in Endothelial Keratoplasty
   • Compare Descemet's Stripping Automated Endothelial Keratoplasty (DSAEK) vs. Descemet's Membrane Endothelial Keratoplasty (DMEK): graft preparation, rebubbling rate, visual outcomes, and endothelial cell loss.
4. Pellucid Marginal Degeneration (PMD)
   • How does PMD differ from keratoconus clinically and topographically? What are the recent management updates?
5. SMILE (Small Incision Lenticule Extraction)
   • What are the biomechanical advantages of SMILE over LASIK? Outcomes in high myopia.
   • What is SILK (smooth incision lenticule keratomileusis)?
6. Targeted Immunomodulatory Therapy in Ocular Surface Disease
   • Ikervis (ciclosporin 0.1% cationic emulsion), lifitegrast (LFA-1/ICAM-1 inhibitor), and dupilumab in chronic ocular surface diseases: mechanisms and evidence (2026 Review).
7. Dry Eye Disease - Chronobiological and Neuroendocrine Advances
   • What is the role of meibomian gland dysfunction chronobiology and neuroendocrine factors (prolactin, androgen deficiency) in dry eye pathogenesis? (Trends Mol Med 2025)

CATARACT & REFRACTIVE SURGERY

1. Advanced Technology IOLs
   • Trifocal vs. extended depth-of-focus (EDOF) IOLs: optical principles, patient selection, and outcomes.
   • Light-adjustable IOL (LAL): how does UV light adjustment work post-implantation? Evidence for accuracy.
   • Accommodating IOLs (Crystalens, FluidVision): current status and limitations.
2. Femtosecond Laser-Assisted Cataract Surgery (FLACS)
   • Compare FLACS vs. conventional phacoemulsification: real-world evidence, cost-benefit, corneal endothelial impact.
3. AI in Cataract Surgery
   • AI-assisted biometry (IOLMaster 700 with AI formulae: Kane, Hill-RBF, Ladas super formula), and AI-based intraoperative guidance systems.
   • Barrett Universal II vs. newer AI formulae in short and long eyes.
4. Presbyopia Correction
   • Corneal inlay options (KAMRA), laser blended vision (Presbyond), and pilocarpine 1.25% eye drops (Vuity) - mechanisms and clinical evidence.

NEURO-OPHTHALMOLOGY

1. LHON (Leber Hereditary Optic Neuropathy)
   • What is the genetic basis (MT-ND4 mutation)? Discuss idebenone (Raxone) and gene therapy (lenadogene nolparvovec/Lumevoq) clinical trial outcomes (2025 Review - Chen & Newman).
2. Emerging Strategies for Optic Nerve Regeneration
   • What pathways are being targeted for optic nerve axon regeneration? (PTEN, SOCS3, Lin28, cAMP-dependent signaling) - Trends Pharmacol Sci 2025.
3. Nystagmus - Diagnosis to Treatment
   • Classify nystagmus (infantile, acquired). What are the current pharmacological (gabapentin, memantine, 4-aminopyridine) and surgical (Anderson/Kestenbaum) options? (Clin Ophthalmol 2025 Comprehensive Review)

OCULOPLASTY & ORBIT

1. Thyroid Eye Disease (TED) - Teprotumumab
   • Mechanism of teprotumumab (IGF-1R inhibitor) in TED. Evidence from OPTIC trial. How does it differ from traditional immunosuppression?
   • What are the side effects, and what is the response in proptosis reduction?
2. Orbital Imaging Advances
   • MRI with fat suppression sequences (STIR, T1 fat-sat) in orbital apex lesions; DWI in orbital lymphoma vs. pseudotumor.

PEDIATRIC OPHTHALMOLOGY

1. Myopia Control - Latest Evidence (2025-2026)
   • Cochrane Network Meta-Analysis 2025 (Lawrenson et al.): rank order of efficacy for myopia control interventions - 0.05% atropine vs. 0.01% atropine vs. orthokeratology vs. MiSight contact lenses vs. DIMS spectacles.
   • FDA authorization (2025): Essilor Stellest spectacle lenses for myopia control in children aged 6-12 years.
   • Repeated Low-Level Red Light (RLRL) therapy: mechanism, Meta-analysis 2025 (Liu et al. Sci Rep) comparing RLRL vs. conventional treatments.
   • Rebound effect with atropine cessation.
2. Retinoblastoma
   • Intra-arterial chemotherapy (IAC) for advanced group D/E retinoblastoma: technique via ophthalmic artery, outcomes, comparison with systemic chemotherapy.
   • Intravitreal melphalan for vitreous seeding.
   • EZH2 and RB1 gene mutations and their role in pathogenesis and genetic counseling.

IMAGING TECHNOLOGIES

1. Swept-Source OCT vs. Spectral-Domain OCT
   • What are the optical and clinical advantages of SS-OCT (deeper penetration, faster A-scan speed, less signal falloff)?
2. Tear Fluid Biomarkers
   • What are the emerging clinical applications of tear fluid biomarkers (lactoferrin, MMP-9, IgE, cytokines, metabolomics)? Methodological approaches (Prog Retin Eye Res 2025 Scoping Review).

ARTIFICIAL INTELLIGENCE IN OPHTHALMOLOGY

1. AI for Diabetic Retinopathy Screening
   • IDx-DR (now LumineticsCore): FDA-cleared autonomous AI for DR screening without an ophthalmologist. Evidence from systematic review (Surv Ophthalmol 2024).
   • What are the ethical challenges and limitations of AI in ophthalmology? (Med Hypothesis 2025)
2. Generative AI and Large Language Models (LLMs) in Ophthalmology
   • What role can LLMs (GPT-4, Gemini) play in ophthalmology - clinical decision support, patient communication, EHR summarization?
   • How can AI transform medical training and residency education? (Lancet Digit Health 2025)

GENETIC ENGINEERING & THE EYE

1. CRISPR-Cas9 in Ophthalmic Disease
   • First in-vivo CRISPR trials for Leber Congenital Amaurosis type 10 (CEP290 mutation) - EDIT-101. What were the outcomes?
   • What are the challenges of in-vivo vs. ex-vivo gene editing for ocular disease? (Eye 2025, Murphy & Martin)
2. Antisense Oligonucleotides (ASOs) and RNA-based Therapies
   • How do ASOs work in CEP290-associated LCA? What is sepofarsen?
   • Distinction between gene replacement, gene editing, and gene silencing approaches.

HIGH-YIELD QUICK-ANSWER TOPICS (Short Notes Format)

EXAM PATTERN TIPS (Based on Dec 2025 DNB)

• Long answer (10 marks): Expect questions on recent anti-VEGF agents (faricimab), MIGS, gene therapy for IRDs, AI in ophthalmology, myopia control, CXL protocols.
• Short notes (5 marks): Complement inhibitors in GA, teprotumumab in TED, OCTA clinical uses, Susvimo, RLRL therapy.
• Viva hotspots: Any FDA approval in the last 2 years is fair game - Stellest lenses, Susvimo for DR, IDx-DR, complement inhibitors.
• Clinical case format: A case of geographic atrophy needing novel therapy; a case of advanced keratoconus requiring surgical options; progressive myopia in a 10-year-old - management options.