Retinal Disease, Glaucoma & Ocular Gene Therapy
A comprehensive analysis of the ophthalmology clinical trial landscape — from optical coherence tomography and intravitreal injection infrastructure to retinal imaging endpoints and pipeline dynamics across anti-VEGF therapies, gene therapy, and novel glaucoma treatments.
The Ophthalmology Trial Landscape in 2026
Ophthalmology clinical research has entered a transformative era defined by the convergence of long-acting anti-VEGF therapies, complement-mediated approaches for geographic atrophy, and gene-based interventions for inherited retinal disease. Within the Clinitiative network, ophthalmology represents a specialized but rapidly growing therapeutic portfolio with 10 active studies spanning wet age-related macular degeneration (AMD), diabetic macular edema (DME), glaucoma, uveitis, gene therapy for inherited retinal diseases, and myopia management. This portfolio reflects both the significant unmet medical need in vision-threatening conditions and the accelerating innovation in ocular drug delivery, imaging-based endpoints, and surgical gene therapy approaches that are redefining what is possible in ophthalmic clinical development.
The distribution of active studies across our network reflects current pipeline dynamics: wet AMD and DME lead with 4 active protocols, driven by extended-durability anti-VEGF formulations and bispecific antibodies targeting VEGF and angiopoietin-2 simultaneously. Glaucoma accounts for 3 studies focused on sustained-release drug delivery implants and novel mechanisms targeting trabecular meshwork function and neuroprotection. Inherited retinal disease gene therapy represents 2 studies, building on the landmark approval of voretigene neparvovec (Luxturna) for RPE65-associated retinal dystrophy and expanding into new genetic targets including RPGR for X-linked retinitis pigmentosa and CNGB3/CNGA3 for achromatopsia. The remaining study addresses posterior uveitis with a novel immunomodulatory approach targeting TNF-alpha and IL-6 pathways.
Anti-VEGF therapy continues to dominate the retinal disease landscape, but the field is shifting decisively toward longer-acting formulations that reduce injection burden — a factor that profoundly impacts both patient quality of life and clinical trial design. Geographic atrophy, the advanced form of dry AMD, has emerged as a major pipeline focus following the approval of pegcetacoplan and avacincaptad pegol, the first complement-based therapies for this condition. Meanwhile, ocular gene therapy is expanding from its proof-of-concept in RPE65 deficiency into a broader portfolio of inherited retinal diseases, requiring vitreoretinal surgical capabilities and specialized post-operative monitoring that push the boundaries of traditional ophthalmic clinical trial infrastructure.
Key Performance Metrics
Network-wide benchmarks from our ophthalmology portfolio provide critical reference points for study planning, site performance evaluation, and enrollment forecasting across ophthalmic indications.
Across all ophthalmology indications, our network sites achieve a median enrollment rate of 1.4 patients per site per month. AMD studies perform above this benchmark at 1.6 patients per site per month, benefiting from the high prevalence of the condition in the aging population and established retina specialist referral pathways. Glaucoma studies achieve 1.8 patients per site per month due to large patient populations with regular intraocular pressure monitoring. Rare inherited retinal disease studies face significant enrollment challenges at 0.4 patients per site per month, reflecting the ultra-rare nature of specific genetic conditions and the need for genetically confirmed diagnoses prior to screening.
Screen failure rates across the ophthalmology portfolio average 30%, with OCT-based retinal thickness criteria and visual acuity thresholds serving as the primary drivers. Wet AMD studies requiring a minimum central subfield thickness on spectral-domain OCT exclude patients whose disease has been well-controlled on existing anti-VEGF therapy. ETDRS visual acuity requirements further narrow the eligible population, particularly in studies targeting early disease stages. DME studies face additional screen failure from hemoglobin A1c exclusion criteria designed to ensure glycemic stability, while glaucoma studies experience lower screen failure rates at 22-25% due to more objective IOP-based eligibility criteria.
From contract execution to first patient enrolled, ophthalmology sites within the network achieve a median startup time of 14.8 weeks. This longer timeline reflects the specialized equipment validation requirements unique to ophthalmic trials, including OCT device calibration and software version standardization across sites, reading center certification for retinal imaging, ETDRS visual acuity chart and lane setup validation, and establishment of central imaging vendor upload pathways. Sites with established retinal imaging core laboratory relationships and prior ophthalmic trial experience consistently achieve startup 3-4 weeks faster than sites undergoing initial imaging certification.
The overall patient retention rate across ophthalmology studies is 82%, with variation driven primarily by treatment burden and patient demographics. Rare inherited retinal disease studies demonstrate the highest retention at 94%, reflecting the profound unmet need in these conditions and the transformative potential of gene therapy. Wet AMD and DME studies maintain moderate retention at 80-83%, with injection fatigue and the elderly patient demographic contributing to dropout. Glaucoma studies retain approximately 81% of patients, with the asymptomatic nature of early glaucoma reducing the perceived urgency of continued trial participation. Transportation challenges in elderly and visually impaired populations represent a consistent retention risk across all ophthalmic indications.
Network Capabilities
Executing ophthalmology trials at the precision and imaging quality required by modern retinal protocols demands highly specialized infrastructure, certified imaging technicians, and operational workflows that integrate seamlessly with central reading centers. Our network has been developed to ensure deep ophthalmology-specific capabilities that meet the rigorous demands of imaging-based endpoints, intravitreal drug delivery, and emerging gene therapy surgical procedures.
Retinal Imaging Suite
Retinal imaging forms the foundation of virtually every retinal disease clinical trial, with optical coherence tomography (OCT) serving as both a screening tool and the primary anatomic endpoint in most wet AMD and DME studies. Our network sites maintain comprehensive retinal imaging suites equipped with spectral-domain OCT (SD-OCT) with enhanced depth imaging capability, OCT angiography (OCT-A) for non-invasive visualization of retinal and choroidal vasculature, fundus autofluorescence (FAF) for geographic atrophy measurement and RPE health assessment, and ultra-widefield photography for peripheral retinal documentation in diabetic retinopathy and retinal vein occlusion studies.
All imaging equipment is maintained on standardized software versions and undergoes annual calibration certification. Imaging technicians complete reading center-specific certification for each protocol, ensuring consistent acquisition parameters including scan pattern, signal strength thresholds, and anatomic centering. Our sites achieve a first-attempt imaging quality acceptance rate exceeding 93% from central reading centers, reducing the need for repeat imaging visits and accelerating endpoint adjudication timelines.
Intravitreal Injection & Treatment Infrastructure
Intravitreal injection is the standard route of administration for the majority of retinal disease therapeutics, and the procedural infrastructure required for clinical trials exceeds that of routine clinical practice. Our network sites maintain dedicated procedure rooms meeting clean-room standards for intravitreal injections, with standardized aseptic protocols including povidone-iodine preparation, sterile draping, and speculum-assisted injection technique. Post-injection monitoring areas accommodate the 15-30 minute observation period required by most protocols for assessment of immediate complications including elevated intraocular pressure, vitreous reflux, and endophthalmitis screening.
For studies evaluating novel drug delivery systems — including port delivery systems requiring surgical implantation, sustained-release intravitreal implants, and suprachoroidal injection techniques — our sites provide the surgical and peri-operative infrastructure necessary for these more complex interventions. Post-procedure monitoring protocols are tailored to the specific delivery mechanism, with appropriate follow-up schedules for complications unique to each approach.
Visual Function Assessment
Visual acuity measurement using ETDRS (Early Treatment Diabetic Retinopathy Study) charts remains the regulatory gold standard for functional endpoints in retinal disease trials. Our network sites maintain ETDRS-certified testing lanes with standardized lighting conditions, calibrated chart distances (4 meters with 1-meter refraction testing), and certified visual acuity examiners who undergo protocol-specific training and annual recertification. Refraction protocols ensure that best-corrected visual acuity is measured consistently across timepoints, eliminating refractive variability as a source of endpoint noise.
Beyond standard visual acuity, our sites support advanced visual function assessments including microperimetry for macular sensitivity mapping in geographic atrophy and inherited retinal disease studies, contrast sensitivity testing using Pelli-Robson and CSV-1000 charts, dark adaptometry for assessing rod photoreceptor function, and full-field and multifocal electroretinography (ERG) for objective measurement of retinal function in gene therapy trials. These assessments require dedicated darkroom facilities, calibrated testing equipment, and technicians trained in the specific protocols required by each study.
Ophthalmic Gene Therapy Capabilities
Ocular gene therapy represents the most technically demanding modality in ophthalmic clinical trials, requiring vitreoretinal surgical expertise, specialized product handling, and intensive post-operative monitoring. Sub-retinal delivery — the standard approach for RPE-targeting gene therapies — involves a three-port pars plana vitrectomy, posterior vitreous detachment induction, retinotomy, and controlled sub-retinal injection using microinjection cannulas with real-time OCT-guided visualization. Our network sites with gene therapy capabilities maintain dedicated operating suites with vitrectomy systems, intraoperative OCT, and the cryogenic storage and thawing protocols required for viral vector product handling.
Post-operative management for gene therapy studies includes intensive monitoring schedules with same-day and next-day examinations, systemic and topical corticosteroid management to control inflammation, serial OCT imaging to monitor sub-retinal fluid resorption, and long-term follow-up for vector-related immune responses. Sites must also maintain protocols for managing potential complications including retinal detachment, macular hole, endophthalmitis, and catarract progression. The surgical and post-operative complexity of gene therapy studies limits eligible sites to those with experienced vitreoretinal surgeons and established peri-operative research infrastructure.
Enrollment Dynamics
Ophthalmology enrollment patterns are shaped by the unique intersection of age-related disease demographics, subspecialty referral pathways, imaging-based eligibility criteria, and the practical challenges of engaging visually impaired and elderly patient populations in clinical research. Understanding these dynamics is essential for realistic enrollment planning across ophthalmic indications.
Wet AMD recruitment benefits from the high prevalence of the condition in the aging population and the established infrastructure of retina specialist practices where patients receive ongoing anti-VEGF injections. However, many active wet AMD patients are well-controlled on current anti-VEGF therapy, making them ineligible for studies requiring active disease with minimum retinal thickness thresholds. Our network addresses this through partnerships with retina practices that identify treatment-naive patients, patients experiencing breakthrough disease on current therapy, and patients transitioning between anti-VEGF agents. DME enrollment leverages diabetes co-management pathways, with referrals from endocrinology and primary care practices identifying patients with clinically significant macular edema requiring treatment escalation.
Glaucoma recruitment draws from established intraocular pressure (IOP) monitoring populations within ophthalmology practices, where patients on topical IOP-lowering therapy represent a readily identifiable pool for studies evaluating novel mechanisms or sustained-release delivery systems. Washout study designs — requiring patients to discontinue current therapy before baseline measurements — introduce complexity around patient safety monitoring during the washout period and contribute to screen failure when post-washout IOP levels do not meet study entry criteria.
Rare inherited retinal disease recruitment represents the most challenging enrollment domain in ophthalmology. Conditions such as X-linked retinitis pigmentosa, achromatopsia, and Stargardt disease affect extremely small populations, and genetically confirmed diagnoses are a prerequisite for study eligibility. Our network recruits these patients through genetic testing registries, inherited retinal disease specialty clinics, patient advocacy organizations (such as the Foundation Fighting Blindness), and international referral networks. Across all ophthalmic indications, the elderly and visually impaired demographics of the patient population necessitate transportation accommodation, accessible facility design, and caregiver engagement strategies that address the practical barriers to sustained trial participation.
Key Challenges in Ophthalmology Trial Execution
The increasing sophistication of ophthalmic protocols presents operational challenges that require specialized strategies, infrastructure, and clinical expertise to address effectively.
Injection Burden & Treatment Fatigue
The standard-of-care for wet AMD and DME requires ongoing intravitreal anti-VEGF injections, with many patients receiving monthly or bimonthly injections for years. This chronic injection burden creates significant treatment fatigue that affects both clinical trial enrollment and retention. Patients may be reluctant to enter studies that require fixed monthly injection schedules when treat-and-extend approaches allow longer intervals in clinical practice. Conversely, studies evaluating longer-acting formulations or alternative delivery systems are highly attractive to injection-fatigued patients. Our network leverages this dynamic by identifying patients experiencing injection burden dissatisfaction as a targeted recruitment channel for extended-durability studies, while maintaining engagement strategies including flexible scheduling, injection comfort optimization, and regular communication about study progress to minimize dropout in fixed-interval protocols.
Imaging Endpoint Complexity
Retinal imaging endpoints require a level of standardization, quality control, and central adjudication that exceeds most other therapeutic areas. Central reading centers mandate specific OCT scan patterns, signal strength thresholds, and segmentation algorithms for measuring central subfield thickness, subretinal fluid, intraretinal fluid, and pigment epithelial detachment dimensions. Fundus autofluorescence imaging for geographic atrophy trials requires precise lesion delineation and growth rate measurement with inter-visit reproducibility within 0.05 mm squared. The complexity of these imaging endpoints means that even minor deviations in acquisition technique can result in ungradeable images, repeat visit requirements, and delays in endpoint adjudication. Our network implements rigorous imaging quality management programs including technician certification by each central reading center, real-time image quality feedback, and dedicated imaging coordinators who review every submission before upload to the central reading center.
Age-Related Comorbidities
The ophthalmology clinical trial population skews heavily toward elderly patients, with the median age of wet AMD trial participants typically exceeding 75 years. This demographic profile introduces significant comorbidity challenges including cardiovascular disease, mobility limitations, cognitive decline, and polypharmacy considerations that complicate both eligibility assessment and study conduct. Falls and fractures, hospitalizations for cardiac events, and cognitive changes affecting informed consent capacity all contribute to study discontinuation in this population. Our network sites implement elderly-friendly clinical trial infrastructure including accessible examination facilities, wheelchair-compatible imaging equipment, reduced visit durations where protocol permits, caregiver engagement programs, and coordination with primary care providers to manage intercurrent medical conditions that might otherwise lead to premature study withdrawal.
Gene Therapy Surgical Requirements
Ocular gene therapy studies require vitreoretinal surgical expertise that limits eligible sites to academic medical centers and specialized retina surgery practices with high-volume vitrectomy experience. The sub-retinal delivery procedure carries inherent surgical risks including retinal detachment, macular hole formation, and the potential for foveal damage during sub-retinal bleb creation. Post-operative steroid management must balance inflammation control with cataract progression risk and systemic immunosuppression considerations. The manufacturing and logistics complexity of viral vector products adds further challenges, with strict cold-chain requirements, limited product shelf life after thawing, and the need for precise surgical timing that coordinates with product preparation. Our network sites with gene therapy capabilities maintain dedicated surgical teams, established product handling protocols, and intensive post-operative monitoring schedules with 24-hour on-call vitreoretinal coverage for management of acute surgical complications.
Pipeline Analysis
The ophthalmology development pipeline is expanding across multiple fronts, with innovation in drug delivery systems, novel mechanisms for previously untreatable conditions, and gene-based therapies driving significant shifts in trial design, site requirements, and enrollment strategies.
Extended-Durability Anti-VEGF
The primary limitation of current anti-VEGF therapy is the need for frequent intravitreal injections, and the pipeline is heavily focused on extending treatment durability. Port delivery systems — surgically implanted refillable reservoirs that continuously release anti-VEGF medication into the vitreous cavity — represent a paradigm shift in drug delivery, enabling treatment intervals of 6 months or longer. High-dose anti-VEGF formulations designed for less frequent injection are progressing through late-phase development, while bispecific antibodies simultaneously targeting VEGF-A and angiopoietin-2 (such as faricimab) are demonstrating extended durability in real-world practice and expanding into new indications. These extended-durability studies require longer follow-up periods, treat-and-extend comparator designs, and sophisticated imaging endpoints that capture both the anatomic and functional benefits of reduced injection frequency.
Geographic Atrophy & Dry AMD
Geographic atrophy (GA), the advanced form of dry AMD, affects approximately 5 million people globally and was historically considered untreatable. The recent approvals of complement inhibitors pegcetacoplan (targeting C3) and avacincaptad pegol (targeting C5) have validated complement-mediated inflammation as a therapeutic target, but these agents slow rather than halt GA progression and require ongoing intravitreal injections. The next wave of GA therapies includes novel complement pathway inhibitors targeting additional nodes in the cascade (factor B, factor D, properdin), RPE cell replacement therapies using stem cell-derived RPE sheets or suspensions, and neuroprotective agents aimed at preserving photoreceptors in areas of expanding atrophy. These studies require precise FAF- based GA lesion measurement, long treatment durations (typically 24 months), and patient populations with documented GA progression rates to demonstrate meaningful treatment effects.
Gene Therapy for Inherited Retinal Disease
Building on the success of voretigene neparvovec for RPE65-associated retinal dystrophy, the gene therapy pipeline for inherited retinal diseases is expanding rapidly. RPGR gene therapy for X-linked retinitis pigmentosa — the most common form of RP in males — is in advanced clinical development, with multiple programs in Phase II and Phase III. Gene therapy approaches for achromatopsia (targeting CNGB3 and CNGA3 mutations), choroideremia (CHM gene replacement), and Stargardt disease (ABCA4 gene augmentation) represent additional programs with active clinical trials. These studies require genetically confirmed diagnoses as an enrollment prerequisite, sub-retinal or intravitreal vector delivery, and functional endpoints including full-field stimulus testing, microperimetry, and mobility maze assessments that capture clinically meaningful visual function improvements in patients with severely limited baseline vision.
Novel Glaucoma Approaches
Glaucoma treatment has been limited to IOP reduction through topical medications, laser trabeculoplasty, and surgical drainage procedures, but the pipeline is expanding into novel mechanisms that address the limitations of current therapy. Sustained-release drug delivery implants — including bimatoprost intracameral implants and travoprost intracameral rings — eliminate daily topical medication adherence challenges by providing continuous IOP lowering for 6-12 months. Gene therapy approaches targeting the trabecular meshwork to enhance aqueous outflow are in early clinical development, offering the potential for durable IOP reduction without ongoing medication. Neuroprotective agents that protect retinal ganglion cells independently of IOP reduction address the unmet need in patients who continue to experience visual field progression despite adequate IOP control. These novel approaches require specialized endpoint assessments including 24-hour IOP monitoring, visual field progression analysis, and OCT-based retinal nerve fiber layer thickness measurement.
Site Requirements for Ophthalmology Excellence
The infrastructure, staffing, and operational processes required to execute modern ophthalmology protocols at the highest level of imaging quality, procedural safety, and regulatory compliance.
Comprehensive retinal imaging suite equipped with spectral- domain OCT with enhanced depth imaging, OCT angiography, fundus autofluorescence, ultra-widefield color photography, and fluorescein/ICG angiography capabilities. Reading center certification for each active protocol, standardized software versions, and dedicated imaging coordinators ensuring quality compliance across all timepoints.
Dedicated procedure room meeting clean-room standards for intravitreal injections, with standardized aseptic protocols, post-injection monitoring area, IOP measurement equipment, and emergency supplies for anaphylaxis and endophthalmitis management. Capacity for fixed-interval injection schedules without displacing standard-of-care treatment volume.
ETDRS-certified testing lanes with standardized lighting conditions, calibrated chart distances, and certified visual acuity examiners. Advanced functional assessment capabilities including microperimetry, contrast sensitivity, dark adaptometry, and electroretinography with dedicated darkroom facilities and calibrated testing equipment.
Vitreoretinal surgical suite equipped with modern vitrectomy systems, intraoperative OCT, microinjection cannula systems for sub-retinal delivery, and cryogenic storage for viral vector products. Experienced vitreoretinal surgical teams with 24-hour on-call coverage and established post-operative monitoring protocols including next-day examination schedules.
Research pharmacy with controlled-temperature storage including cryogenic capabilities for gene therapy vectors, intravitreal injection preparation protocols under aseptic conditions, drug accountability systems, and pharmacist oversight of investigational product reconstitution, dilution, and preparation timing to ensure product viability at the point of administration.
Dedicated ophthalmic clinical research coordinators with retina-specific training, certified imaging technicians with reading center-specific credentials, ophthalmic research nurses experienced in injection suite protocols, vitreoretinal surgeons for gene therapy studies, and regulatory coordinators managing IRB submissions and protocol amendments across multiple active ophthalmic protocols.
Discuss Your Ophthalmology Program
Connect with our team to explore site capabilities, enrollment strategies, and retinal imaging infrastructure for your ophthalmology clinical development program.