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EXUDATIVE AND TRACTIONAL RETINAL DETACHMENT

A Comprehensive Clinical Review — Basic to Advanced

PART 1: FOUNDATIONS

1.1 What is Retinal Detachment?

1.2 What Normally Keeps the Retina Attached?

• RPE fluid pump: The RPE actively transports ions (especially Cl⁻) into the choroid, creating an osmotic gradient that draws fluid from the subretinal space outward. This is the most important mechanism.
• Choroidal osmotic pressure: The high protein content of choroid relative to subretinal space creates an oncotic gradient that draws water outward.
• Interphotoreceptor matrix (IPM): A gel-like matrix fills the space between photoreceptors and RPE, providing a mechanical adhesion layer.
• Intraocular pressure (IOP): The outward pressure of the vitreous and aqueous gently pushes the retina against the RPE.

1.3 Classification of Retinal Detachment

Key teaching point: Both exudative and tractional RD lack retinal breaks as a primary feature. This is the single most important clinical distinction from rhegmatogenous RD.

PART 2: EXUDATIVE (SEROUS) RETINAL DETACHMENT

2.1 Definition

2.2 Pathophysiology

The Blood-Retinal Barrier (BRB)

• Inner BRB (iBRB): Tight junctions (zonula occludens) between retinal vascular endothelial cells. Prevents plasma from leaking out of retinal capillaries.
• Outer BRB (oBRB): Tight junctions between adjacent RPE cells. Prevents choroidal plasma from crossing into the subretinal space.

Two mechanisms of exudative RD:

1. Hypersecretion: Excessive fluid production from abnormal choroidal or retinal vessels (e.g., choroidal melanoma, Coats disease, choroidal neovascularisation)
2. Defective transport: Impaired RPE pump function, so even normal amounts of fluid cannot be cleared (e.g., RPE disease, photoreceptor toxicity)

Hallmark feature — Shifting subretinal fluid:

2.3 Aetiology — Causes of Exudative RD

A. Neoplastic Causes

• Circumscribed: Benign, isolated, orange-red elevated lesion at the posterior pole. Slowly enlarges, causing exudative RD with chronic SRF and progressive vision loss.
• Diffuse: Associated with Sturge-Weber syndrome (port-wine stain, glaucoma, leptomeningeal angioma). The entire choroid is thickened, causing massive exudative RD from childhood.

B. Inflammatory and Infectious Causes

1. Prodromal stage (3-5 days): Headache, fever, nausea, meningism, tinnitus, hearing loss
2. Uveitic stage (weeks): Bilateral granulomatous anterior uveitis, posterior uveitis, multifocal serous RD, disc hyperaemia, subretinal folds ("Dalen-Fuchs nodule" equivalent in posterior pole)
3. Convalescent stage (months): Sunset glow fundus (diffuse choroidal depigmentation), perilimbal vitiligo (Sugiura sign), skin vitiligo, poliosis, alopecia
4. Chronic recurrent stage: Recurrent anterior uveitis, cataract, glaucoma

• Syphilis: Secondary/tertiary syphilis causes posterior uveitis, necrotising retinitis, and exudative RD. Serological testing (VDRL + FTA-ABS) is mandatory in any unexplained uveitis.
• Leptospirosis: Weil's disease; uveitis and exudative RD weeks after systemic illness.
• Brucella: Rare cause of posterior uveitis and exudative RD in endemic areas.

• Herpesvirus family: HSV, VZV, and CMV are the most important. Acute Retinal Necrosis (ARN) from HSV/VZV presents with peripheral necrotising retinitis, vitritis, arteritis, and exudative RD. CMV retinitis in AIDS patients shows the "brush-fire" or "pizza-pie" appearance (haemorrhage + white necrosis) with exudative components.

• Candida endophthalmitis: IV drug users, immunocompromised patients, post-surgical. White fluffy vitreous balls ("string of pearls"), focal choroiditis with SRF.
• Toxocara canis: Children. Solitary granuloma at posterior pole or peripheral retina with exudative RD. Very high peripheral eosinophilia.
• Toxoplasmosis: Focal necrotising retinochoroiditis ("headlight in the fog" appearance), may cause localised exudative RD adjacent to active lesion.

C. Vascular Causes

• Stage 1: Telangiectasias only
• Stage 2: Telangiectasias + exudates (2A: extrafoveal, 2B: foveal)
• Stage 3: Partial (3A) or total (3B) exudative RD
• Stage 4: Total RD + glaucoma
• Stage 5: End-stage (phthisis)

D. Iatrogenic and Miscellaneous Causes

• Post-retinal surgery: Scleral buckling or encircling procedures can cause choroidal effusion that leaks into the subretinal space postoperatively
• Panretinal photocoagulation (PRP): Extensive PRP can cause transient exudative RD by disrupting the outer BRB at laser impact sites
• Drug-induced: Interferon-alpha + ribavirin (used in hepatitis C treatment) causes exudative RD via RPE toxicity — resolves on drug discontinuation combined with corticosteroids
• Nanophthalmos: Abnormally short, thick-walled eye with impaired vortex vein drainage, causing uveal effusion and exudative RD
• Uveal Effusion Syndrome: Idiopathic, predominantly middle-aged males. Abnormally thick or rigid sclera impedes choroidal venous outflow through vortex veins, causing bilateral serous choroidal detachment, ciliary body detachment, and exudative RD. Treatment: sclerectomy/sclerotomy.
• Optic Nerve Pit: A congenital defect in the optic nerve head. CSF-like fluid (origin debated) tracks from the optic pit through the outer retina into the subretinal space, causing characteristic macular detachment with schisis.

2.4 Clinical Features and Diagnosis

Symptoms

• Visual field defect: May appear suddenly and progress rapidly — more acute than tractional RD
• Blurred vision / metamorphopsia: When SRF reaches or threatens the macula
• Floaters: Present only if there is associated vitritis (e.g., VKH, posterior scleritis, infection)
• Photopsia (flashing lights): ABSENT — there is no acute posterior vitreous detachment tearing at the retina
• Bilateral involvement: Both eyes may be affected simultaneously (VKH, malignant hypertension, bilateral metastases)
• Systemic symptoms: Headache and tinnitus in VKH; pain on eye movement in scleritis; history of cancer in metastases

Signs

Investigations

• VKH: Multiple early hyperfluorescent pinpoint leaks at the RPE level, pooling into bullous serous RD in late frames
• CSC: Single (or few) focal "hot spot" of leakage at the RPE, expanding in late frames
• Choroidal tumour: Intrinsic tumour vasculature; hot spots in haemangioma; late leakage in melanoma
• Posterior scleritis: Disc leakage, pinpoint leaks, late pooling

2.5 Treatment of Exudative RD

Inflammatory causes (VKH, Posterior Scleritis, Sympathetic Ophthalmia)

• IV methylprednisolone pulse (1 g/day for 3 days) followed by oral prednisolone (1-1.5 mg/kg/day) tapering over 6-12 months — the exudative RD in VKH resolves dramatically within days of adequate corticosteroid treatment
• Steroid-sparing immunosuppression: Azathioprine (1-2 mg/kg/day), mycophenolate mofetil (1-1.5 g twice daily), or cyclosporine for recurrent/refractory cases or when steroids cannot be tapered
• For posterior scleritis: NSAIDs as adjunct; periocular/systemic steroids; immunosuppression for refractory cases

Neoplastic causes

• Circumscribed choroidal haemangioma: Photodynamic therapy (PDT) with verteporfin is first-line — 85-95% complete SRF resolution with a single session (Yang et al. Surv Ophthalmol 2025, PMID 39862992). Alternatives: brachytherapy, transpupillary thermotherapy (TTT), intravitreal anti-VEGF as adjunct
• Choroidal melanoma: Ruthenium-106 plaque brachytherapy (tumours <10 mm height); proton beam radiotherapy; enucleation for large tumours (>10 mm height, ≥16 mm base). Collaborative Ocular Melanoma Study (COMS) established equivalent survival between brachytherapy and enucleation for medium-sized melanoma.
• Choroidal metastases: Systemic chemotherapy/hormonal therapy for the primary tumour; external beam radiotherapy (20-30 Gy) for the ocular lesion; intravitreal anti-VEGF as adjunct for anti-exudative effect
• Intraocular lymphoma: Intravitreal methotrexate (400 micrograms/0.1 mL twice weekly x 4 weeks then maintenance); external beam radiotherapy; systemic high-dose methotrexate for CNS involvement

Vascular causes

• Coats disease: Laser photocoagulation (argon or micropulse 577 nm) or cryotherapy to telangiectatic vessels; intravitreal anti-VEGF (bevacizumab/ranibizumab) as adjunct to reduce vascular leakage; vitrectomy + drainage of SRF + silicone oil for advanced Stage 3B-4 disease (Ucgul & Ozdek, Semin Ophthalmol 2025, PMID 40094375)
• Malignant hypertension: Urgent antihypertensive therapy (IV labetalol, oral amlodipine/ACE inhibitor); SRF resolves spontaneously with BP control
• Pre-eclampsia: Delivery; magnesium sulphate; antihypertensives; SRF resolves within weeks postpartum
• CSC (acute): Observation for 3 months — 80% spontaneous resolution. If persistent: focal laser photocoagulation to RPE leaking point (if extrafoveal); half-dose/half-fluence PDT (most effective for chronic CSC); intravitreal bevacizumab; eplerenone 25-50 mg/day (mineralocorticoid receptor antagonist — VICI trial evidence); spironolactone as alternative (Kim et al. Eye 2025, PMID 40615611)

Uveal effusion syndrome

PART 3: TRACTIONAL RETINAL DETACHMENT

3.1 Definition

3.2 Pathophysiology

1. Tangential traction: Membranes contract parallel to the retinal surface, causing retinal puckering, vascular distortion, and tractional macular schisis
2. Anteroposterior (AP) traction: Membranes extend from posterior retina to the vitreous base anteriorly, pulling the retina forward like a tent pole, creating a tent-shaped or triangular detachment
3. Bridging (trampoline) traction: Membranes stretch between two retinal locations (e.g., optic disc to temporal arcade), pulling both points toward each other, creating a concave hammock-like detachment

3.3 Aetiology — Causes of Tractional RD

Proliferative Diabetic Retinopathy (PDR) — Most Common

Retinopathy of Prematurity (ROP)

Penetrating Posterior Segment Trauma

Sickle Cell Retinopathy

Branch Retinal Vein Occlusion (BRVO)

Familial Exudative Vitreoretinopathy (FEVR)

3.4 Clinical Features and Diagnosis

Symptoms

• Gradual, progressive visual field loss: The most common presentation. Because PVD in diabetic eyes is incomplete and the retina detaches slowly, many patients describe a gradually encroaching shadow rather than a sudden curtain. The field defect may remain stable for months or even years if the TRD is peripheral and macula-sparing.
• Decreased central vision: The most alarming symptom — signifies that TRD has reached or is threatening the macula. This is a surgical emergency.
• Photopsia: ABSENT in uncomplicated TRD. There is no acute PVD to mechanically stimulate the retina. (Photopsia appearing in a known TRD patient should raise concern for conversion to TRD-RRD.)
• Floaters: Usually absent unless vitreous haemorrhage from traction on NV vessels occurs (which itself may be the presenting symptom that leads to detection of the underlying TRD).

Signs on Fundoscopy

Investigations

• Extent and location of traction
• Presence and depth of subretinal fluid under the macula
• Macular tractional schisis before overt detachment
• Integrity of photoreceptor ellipsoid zone (prognostic for post-surgical visual recovery)
• Identifies whether the TRD is macular-on or macular-off

3.5 Surgical Management of Tractional RD

Indications for Surgery

Preoperative Preparation

• Systemic optimisation: HbA1c <7% (caution: rapid glycaemic optimisation can temporarily worsen diabetic retinopathy); blood pressure control; renal function assessment (contrast dye for FA)
• Ophthalmic assessment: BCVA, IOP, anterior segment (rubeosis iridis — neovascularisation of iris — indicates severe ischaemia and poor prognosis), fundus documentation, B-scan

Preoperative Anti-VEGF Therapy

1. Reduction in fibrovascular membrane vascularity — NVD/NVE shrink, become white and fibrotic within 48-72 hours, dramatically reducing intraoperative bleeding
2. Facilitated membrane dissection — Surgeons can peel membranes with less haemorrhage at membrane-retina interfaces
3. Reduced early postoperative vitreous haemorrhage (POVCH)
4. Potentially shorter operating time and reduced need for silicone oil

• Pre/intraoperative anti-VEGF improved BCVA at 6 months: MD -0.25 logMAR (95% CI: -0.39 to -0.11)
• Reduced early POVCH: 12% vs 31% (RR 0.38)
• Reduced revision surgery rates
• Low-certainty evidence (significant heterogeneity between studies)

Critical timing caveat — "Anti-VEGF Crunch Syndrome": If vitrectomy is delayed >10-14 days after anti-VEGF injection, the VEGF withdrawal accelerates fibrosis of membranes, causing sudden membrane contraction that can convert a pure TRD into a combined TRD-RRD ("crunch"). A 2026 competing-risks analysis (Zhan et al. Ophthalmol Retina, PMID 41475681) confirmed the optimal window is 3-7 days.

Pars Plana Vitrectomy (PPV) — The Gold Standard

• Delamination: Horizontal cutting at the membrane-retina interface, separating the membrane from the retinal surface in a plane
• Segmentation: Vertical cuts through the membrane, dividing it into smaller pieces that relieve tangential traction, leaving small membrane islands
• En-bloc dissection: Used for tight AP traction — detaches the entire membrane-vitreous complex

• Gas (C₃F₈ 12-16%, SF₆ 20%): Absorbed over 2-8 weeks; requires face-down positioning
• Silicone oil (1,000 or 5,000 centistokes): Permanent internal tamponade; useful for complex TRD, PVR, or patients unable to posture; requires later removal (usually 3-6 months)

Postoperative Management

• Positioning: Face-down for superior gas tamponade; lateral for inferior pathology; sitting upright for silicone oil
• IOP monitoring: Silicone oil can cause raised IOP; steroid eye drops cause steroid-response glaucoma; hypotony from wound leak is also possible
• Complication surveillance: Neovascular glaucoma (most serious long-term complication — Cao et al. BMC Ophthalmol 2025, PMID 40155830), recurrent TRD, ERM, nuclear sclerotic cataract, silicone oil emulsification
• Anti-VEGF injections: Postoperative intravitreal anti-VEGF for concurrent diabetic macular oedema (DME) should be resumed once the retina is stable

PART 4: COMPARISON — EXUDATIVE VS TRACTIONAL RD

PART 5: KEY CLINICAL TRIALS

5.1 For Tractional RD (PDR)

• Design: RCT, 305 eyes with PDR; ranibizumab 0.5 mg (with deferred PRP) vs prompt PRP
• Key findings: Ranibizumab non-inferior to PRP for BCVA at 2 years (+2.8 vs +0.2 letters). At 5 years: anti-VEGF group had significantly fewer new TRD cases (9% vs 23%), fewer vitrectomies, better peripheral visual fields, and less DME. Anti-VEGF reduces the burden of PDR complications leading to TRD.

• Design: Phase 3 RCT, 232 eyes; aflibercept 2 mg 2q8 weeks vs PRP
• Key findings: Aflibercept was superior to PRP (not just non-inferior): +3.5 letters vs -0.3 letters at 52 weeks. Significantly fewer VH events and lower TRD rates in the aflibercept arm. Confirmed anti-VEGF as alternative first-line treatment to PRP for PDR.

• Design: Systematic review of 28 RCTs, 1,914 eyes; pre/intraoperative anti-VEGF vs vitrectomy alone for PDR complications (VH, TRD, combined TRD-RRD)
• Key findings: Pre-op anti-VEGF improved BCVA at 6 months (MD -0.25 logMAR); early POVCH reduced from 31% to 12%; reduced revision surgery; no significant increase in combined TRD-RRD risk within the 3-7 day window. Level 1 evidence supporting routine pre-op anti-VEGF.

• Design: Comparative study using large US registry; anti-VEGF vs PRP as initial therapy for PDR
• Key findings: Anti-VEGF as initial therapy significantly reduced progression to pars plana vitrectomy for TRD complications. Real-world confirmation of Protocol S findings.

• Design: Competing-risks analysis of large cohort; timing of pre-op anti-VEGF before vitrectomy for PDR
• Key findings: Optimal timing is 3-7 days; >14 days significantly increases risk of combined TRD-RRD via crunch syndrome. Supports a structured anti-VEGF-to-surgery pathway.

• Design: First dedicated RCT evaluating ILM peeling during vitrectomy for diabetic TRD
• Key findings: ILM peeling group had significantly lower rate of recurrent ERM; no statistically significant BCVA difference at 12 months. Supports ILM peeling as a strategy to reduce re-operation rates for ERM.

• Design: Systematic review and meta-analysis of FEVR-related RD surgical outcomes
• Key findings: Vitrectomy combined with scleral buckling provides best anatomical outcomes for FEVR-associated TRD; recurrence risk 18-28%; early surgery is critical.

5.2 For Exudative RD

• Design: RCT comparing brachytherapy vs enucleation for medium choroidal melanoma
• Key findings: No significant difference in 5-year or 10-year mortality between brachytherapy and enucleation. Established brachytherapy as eye-sparing equivalent to enucleation for medium melanomas.

• Design: Systematic review of treatment outcomes for CCH causing exudative RD
• Key findings: PDT with verteporfin achieves complete SRF resolution in 85-95% with a single treatment. Anti-VEGF monotherapy shows moderate but inferior SRF reduction. PDT remains first-line.

• Design: Phase 3 RCT; eplerenone 25 mg/day vs placebo for chronic CSC
• Key findings: Eplerenone significantly reduced SRF and CSC recurrence vs placebo. Now recommended as pharmacological treatment for chronic CSC (Kim et al. Eye 2025, PMID 40615611).

• Multiple prospective studies and RCTs confirmed: half-dose/half-fluence PDT (verteporfin 0.25 mg/m² or standard dose at 25 J/cm²) resolves SRF in >80% of chronic CSC cases with a single treatment. Lower risk of RPE atrophy vs standard fluence PDT.

• Design: Case report + literature review
• Key findings: Bilateral exudative RD secondary to retinitis pigmentosa successfully resolved with intravitreal aflibercept injections — expanding the role of anti-VEGF to unusual causes of exudative RD.

PART 6: RECENT ADVANCES (2023-2026)

6.1 Imaging Advances

• Deep learning algorithms trained on fundus photography detect early PDR changes (NVD, NVE, fibrovascular proliferation) with sensitivity comparable to retina specialists, enabling earlier intervention before TRD develops
• AI-based OCT segmentation automatically quantifies SRF volume, fibrovascular membrane area, and choroidal thickness in exudative RD — provides objective, reproducible monitoring
• Predictive algorithms integrating systemic data (HbA1c, duration of diabetes, blood pressure) with imaging data forecast TRD risk within 2 years, supporting pre-emptive laser or anti-VEGF treatment

6.2 Pharmacotherapy Advances

• RGX-314 (REGENXBIO): AAV8 vector encoding the ranibizumab Fab fragment delivered subretinally. Transduced RPE cells continuously secrete anti-VEGF protein. Phase 3 ATMOSPHERE trial (nAMD) and ASCENT trial (PDR) are ongoing as of 2025-2026. Phase 2 data showed dose-dependent VEGF suppression maintained for >3 years in some patients.
• 4D-150 (4D Molecular Therapeutics): Engineered intravitreal AAV vector that co-encodes anti-VEGF-A + anti-VEGF-C constructs. Phase 3 4FRONT-1 trial enrolled its first patients in March 2025 for nAMD. Phase 2 PRISM-100 data showed 73% of patients maintained BCVA without monthly injections. If proven in PDR trials, could potentially prevent the progression from PDR to TRD by providing sustained VEGF suppression from a single injection.
• Odio-Herrera et al. review (J Clin Med 2025, PMID 40364236): Comprehensive review of gene therapy in diabetic retinopathy — AAV-mediated VEGF suppression at the gene level may provide year-long suppression per treatment, fundamentally changing the management paradigm for PDR and TRD prevention.

• Suprachoroidal axitinib (CLS-AX): ODYSSEY Phase 2b trial (2025) data showed sustained VEGF suppression for up to 6 months per suprachoroidal injection — potential to dramatically reduce injection frequency in PDR management
• Migaldendranib: Anti-VEGF/PDGFR-beta bispecific small molecule; positive Phase 2 data presented at Angiogenesis 2025 for exudative neovascular retinal disease

6.3 Surgical Advances

PART 7: PROGNOSIS

Exudative RD

• Excellent when underlying cause is treated early — VKH-related serous RD resolves within days of adequate corticosteroid therapy; malignant hypertension-related RD resolves with BP control
• Inflammatory causes: Full visual recovery is possible if treatment begins before macular photoreceptor degeneration occurs
• CSC: 80-90% spontaneous resolution in acute cases within 3 months; 5-10% develop chronic CSC with permanent central scotoma from RPE atrophy
• Tumour-related: Variable — ocular prognosis depends on tumour type, size, and whether the macula has been chronically detached; systemic prognosis is independent
• Poor prognostic factors: Duration of macular detachment >3 months, submacular fibrosis, RPE tears, significant photoreceptor loss (disrupted ellipsoid zone on OCT)

Tractional RD

• Guarded — critically dependent on macular involvement at presentation and duration
• Macular-off TRD: Visual acuity rarely recovers beyond 6/60 if macular detachment has persisted >6 months. Prompt surgery within 7-10 days of macular involvement gives the best chance.
• Macular-on TRD: With prompt vitrectomy, BCVA of 6/12 or better is achievable in 60-70% of eyes
• Anatomical re-attachment: Achieved in 85-95% with modern small-gauge vitrectomy techniques
• Long-term complications affecting prognosis: neovascular glaucoma (Cao et al. BMC Ophthalmol 2025), recurrent TRD (10-15%), ERM formation, cataract progression, silicone oil emulsification
• Systemic control is paramount: Tight glycaemic control (HbA1c <7%) and blood pressure management are the most important factors in preventing TRD recurrence after successful surgery

PART 8: KEY MNEMONICS AND TAKE-HOME POINTS

Mnemonic — Exudative RD: "SHIFT"

• S — Smooth retinal surface (not corrugated)
• H — High retinal mobility (undulates freely)
• I — Inflammation / Infiltration / Iatrogenic — common causes
• F — Fluid shifts with gravity (pathognomonic)
• T — Tumour must always be excluded first

Mnemonic — Tractional RD: "TAUT"

• T — Tethered, taut retina with reduced mobility
• A — Absent shifting fluid, absent photopsia
• U — Underlying fibrovascular membranes cause traction
• T — Timely vitrectomy is the treatment (macular-off = emergency)

Key Points

1. Both exudative and tractional RDs lack retinal breaks — this is their single most important shared feature distinguishing them from rhegmatogenous RD
2. Shifting SRF is pathognomonic for exudative RD; its absence in a non-rhegmatogenous RD points to traction
3. Always exclude choroidal tumour as the cause of exudative RD before attributing it to inflammation, CSC, or any other diagnosis
4. Pre-op anti-VEGF 3-7 days before vitrectomy for PDR-related TRD is Level 1 evidence (Cochrane 2023, 28 RCTs) — reduces BCVA deficit, halves vitreous haemorrhage risk
5. Macular-off TRD is a surgical emergency — vitrectomy within 7-10 days
6. The "crunch syndrome" is a real risk if anti-VEGF is given and surgery delayed >14 days — stick to the 3-7 day window
7. Gene therapy (RGX-314, 4D-150) is in Phase 3 trials and could prevent TRD from PDR by providing sustained VEGF suppression from a single treatment session
8. Faricimab and TKIs address the Ang-2/VEGF dual pathway and PDGFR, offering more durable vascular stabilisation than previous anti-VEGF monotherapy

REFERENCES

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3. Bowling B. Kanski's Clinical Ophthalmology: A Systematic Approach. 10th ed. Elsevier; 2023.
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10. Abu Serhan H, et al. FEVR-associated RD: systematic review. Int J Retina Vitreous. 2026. PMID 41965841.
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13. Odio-Herrera M, et al. Gene therapy in diabetic retinopathy. J Clin Med. 2025. PMID 40364236.
14. Chen-Li G, et al. Angiopoietin-Tie signalling in diabetic retinopathy. J Clin Med. 2024. PMID 38792322.
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16. Ucgul AY, Ozdek S. Coats disease: pathophysiology and treatment advances. Semin Ophthalmol. 2025. PMID 40094375.
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