Bart P Leroy1
Aleman, Tomas S2, 3; Bedoukian, Emma3, 4; Bennett, Jean2; Maguire, Albert M.2
1. Dept of Ophthalmology & Ctr for Medical Genetics, Ghent University Hospital & Ghent University, Ghent, Belgium
2. Scheie Eye Institute, Univ Of Pennsylvania, Philadelphia, PA, USA
3. Division Of Ophthalmology, Children’s Hospital Of Philadelphia, Philadelphia, PA, USA
4. Roberts Individualised Medical Genetics Center, Children’s Hospital Of Philadelphia, Philadelphia, PA, USA

Purpose: to illustrate our experience with voretigene neparvovec for RPE65-related inherited retinal dystrophies (IRD) at the Children’s Hospital of Philadelphia and Scheie Eye Institute of the University of Pennsylvania.

Methods: patients with RPE65-related IRDs underwent pre- and postoperative evaluations including best-corrected visual acuity, Goldmann visual fields, full-field sensitivity testing, full-field flash electroretinography and imaging with blue and infrared reflectance and autofluorescence imaging as well as spectral-domain optical coherence tomography.

Results: at this time, 9 individual patients have been treated with voretigene neparvovec. All have significant improvements in several parameters.

Conclusions: voretigene neparvovec is a safe and efficient treatment, which significantly improves quality-of-Life for patients with RPE65-related IRDs.

Conflict of interest disclosure: The following conflict(s) of interest must be disclosed:
The authors received research support grants and travel grants from Spark Therapeutics & Novartis Pharma

Arlene Drack1
Bennett, Jean2; Russell, Stephen1; High, Katherine A.5; Yu, Zi-Fan4; Tillman, Amy4; Chung, Daniel5; Reape, Kathleen Z.5; Ciulla, Thomas5; Maguire, Albert M.2, 3
1. University of Iowa, Iowa City, IA
2. Children’s Hospital of Philadelphia, Philadelphia, PA
3. Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA
4. Statistics Collaborative, Inc., Washington, DC
5. Spark Therapeutics, Inc., Philadelphia, PA

Introduction: Voretigene neparvovec (VN) gene therapy improves ambulatory navigation, light sensitivity, and visual field in subjects with RPE65–associated Leber Congenital Amaurosis /Inherited Retinal Disease.1 We report Year 4 results for original intervention (OI) subjects, Year 3 for delayed intervention (DI), and Y1 results by age <=10, 11-17, or > 18 years at treatment.

Methods: Subjects were randomized to either original intervention (OI: bilateral subretinal VN at baseline) or delayed intervention (DI: VN after 1 year). Primary endpoint was change in bilateral performance on the Multi-Luminance Mobility Test (MLMT). One of the secondary endpoints was change in full-field light sensitivity threshold (FST) testing.

Results: At Y1, there were no statisically significant differences in MLMT between subjects aged ≤10 (n=13), 11–17 (n=7), and ≥18 years (n=9), however FST was statistically significantly better in those treated at 11-17 vs. ≥18 years. Mean changes in MLMT at Y1 were maintained at Y4 for OI and Y3 for DI. When compared to Y1, 5 subjects (ages at treatment 4, 6, 11, 11, and 34 years) lost a light level while 1 subject (age at treatment 16 years) gained a light level. No subject declined below baseline. One subject had a retinal detachment detected at Y4.

Discussion: Amblyopia may not be a major hindrance to gene therapy treatment but loss of photoreceptors over time may affect outcome.

Conclusions: Functional vision is stable in 24 of 28 (86%) patients from one year post-treatment through the duration of follow-up.

References:
1. Russell S, Bennett J, Wellman JA, et al. Efficacy and safety of voretigene neparvovec (AAV2-hRPE65v2) in patients with RPE65-mediated inherited retinal dystrophy: a randomised, controlled, open-label, phase 3 trial. Lancet. 2017;390(10097), 849-860.
Funding Statement: This study was sponsored by Spark Therapeutics.

Conflict of interest disclosure: The following conflict(s) of interest must be disclosed:
Arlene Drack reports grants from Spark Therapeutics, ProQr, REtrophin and educational fees from Retrophin. Stephen Russell reports consulting fees and grants from Spark Therapeutics, Inc. Jean Bennett reports grants from the Foundation Fighting Blindness, NIH, and Spark Therapeutics, Inc. Zi-Fan Yu and Amy Tillman provided statistical consulting to Spark Therapeutics, Inc. through their employer, Statistics Collaborative, Inc. Katherine A. High, Thomas Ciulla, Daniel Chung, and Kathleen Z. Reape are employees of Spark Therapeutics, Inc. and hold equity in the company. Albert M. Maguire reports grants from the Foundation Fighting Blindness and Spark Therapeutics, Inc.

Arlene Drack
Bhattarai, Sajag; Russell, Stephen; Pfeiffer, Wanda
University of Iowa, Iowa City, IA

Purpose: In animal models of RPE65-mutation associated IRD, ERG response may be restored after subretinal treatment with voretigene neparvovec (Luxturna) but similar recovery has not been documented in humans, even when measures of functional vision such as mobility course and FST improve. We instituted a protocol of electrophysiology testing in patients with LCA to detect if ERG recovers.

Methods: Two female children with RPE65-mutation associated LCA received a battery of electrophysiologic testing including full field ERG, multifocal ERG, and flash VEP in addition to standard clinical studies.

Results: Both patients were 4-years-old at time of treatment. Patient 1 had essentially non- recordable full field and multifocal ERG after treatment but recordable flash VEP. Visual acuity was 20/40 OU after treatment. Patient 2 had essentially nonrecordable flash ERG and flash VEP before treatment, and almost normal amplitude full field ERG and flash VEP after treatment. Visual acuity was 20/100+1 OD and 20/80-1 OS.

Conclusions: Some patients have a marked improvement in electrophysiology following Luxturna. Based on a small sample, flash VEP may be more consistently improved than ERG. Long term follow up may aid in assessing durability of response.

Conflict of interest disclosure: none

Francesca Simonelli
Eye Clinic, Multidisciplinary Department of Medical, Surgical and Dental Sciences, University of Campania Luigi Vanvitelli, Naples, Italy

LCA/Retinal dystrophy caused by mutations in the RPE65 gene is the first ocular disease treated successfully with gene therapy in phase I/II and III clinical trials.
The results obtained in the clinical trials led to the recent approval of the drug voretigene/neparvovec, named Luxturna, by EMA and FDA.

Our experience in phase I/II clinical trial of gene therapy in five Italian patients affected by RPE65 LCA-Retinal dystrophies will be reported showing the results in terms of safety and efficacy. Finally, on the basis of our experience, critical issues arisen in gene therapy clinical trials will be discussed.

Conflict of interest disclosure: The following conflict(s) of interest must be disclosed:
Francesca Simonelli received honorary or consultation fees from Spark Therapeutics, Inc.

Birgit Lorenz
Department of Ophthalmology, Justus-Liebig-University Giessen, Giessen, Germany

Purpose: to report our experience at a designated Luxturna treatment center in Germany preparing to treat the first patients with IRDs associated with biallelic mutations in RPE65.

Methods and Results: Introduction of new therapies requires a complex process in Germany. First, approval by a procedure called NUB – Neue Untersuchungs- und Behandlungsmethoden (new examination and treatment methods) has to be obtained prior to getting approval by the individual health insurance companies of the selected patients. In parallel, the infrastructure for preparing the drug have to be established at the pharmacy of the university clinic. Due to the novel character of the therapy, uncertain legislation with regard to how to handle gene therapeutic medication, and the lack of experience of the involved personnel, establishing a dedicated room and putting trained personnel in place at the pharmacy can become a major hurdle. Furthermore, as the volume of the ready-to-use preparation of Luxturna® is about 5 times the actual substance injected at the level of the interface between RPE and neuroretina, health insurance companies are considering to suggest the usage of one vial for more than one patient.

Conclusion: Approval of a new medication by the EMA does not mean that clinical centers can start immediately with treating patients in Germany but a number of issues need to be solved.

Conflict of interest disclosure: The following conflict(s) of interest must be disclosed:
Birgit Lorenz received honorary or consultation fees from Novartis Pharma, Switzerland

Daniel C. Chung
Spark Therapeutics, Inc., Philadelphia, PA

Following its marketing approval by the FDA in 2017, voretigene neparvovec-rzyl has been administered exclusively at designated Ocular Gene Therapy Treatment Centers (OGTTCs) in the United States (US). This model not only supports the safe storage, preparation and administration of this novel gene therapy, but also facilitates the review of product safety in a larger population than was available in the clinical development program. More than 20 vitreoretinal surgeons are now trained in the administration procedure at ten OGTTCs in the US – compared to 5 surgeons (2 primary, 3 secondary) at two trial sites during the clinical development of voretigene neparvovec-rzyl. The Post-Authorization Safety Study (PASS) is a multicenter, longitudinal, observational safety registry study for patients treated with voretigene neparvovec-rzyl; the planned US enrollment is ≥40 participants and patients will be followed for a period of 5 years. The purpose of the PASS is to evaluate the long-term safety profile of voretigene neparvovec-rzyl for the 5-year post-administration period; all adverse events, information about pregnancy outcomes, and ophthalmic examination results will be collected. Prior to the enrollment of subjects into the PASS, spontaneously reported adverse events occurring during the first year of availability in the US have been collected, summarized and reviewed, and compared to observed rates in the clinical trial. The PASS will collect additional safety data as patients are enrolled in the study.

Conflict of interest disclosure: The following conflict(s) of interest must be disclosed:
Daniel Chung is stock shareholder of Spark Therapeutics, Inc.

Laurence Desjardins
Institut Curie, Rochefort En Yvelines, France

Children with retinoblastoma face very different situations and problems according to the place where they are born. In developed countries survival is excellent and conservative management has made significant improvment with intraarterial and intravitreal chemotherapy.

Nervertheless we observe a worrying increase of metastasis in unilateral retinoblastomas due to excessive indications of conservative management versus enucleation. In developing countries survival is still poor due to late diagnosis and lack of hospital structures able to treat the patients with also financial difficulties for the parents. This is particularly true in sub saharan africa while South America, cChina and Asia have already improved the quality of diagnosis and care in many countries. The AMCC programm aims to improve diagnosis and treatment of retinoblastoma in Sub Saharan Africa where the natality is still very high (4,9) with approximatively one thousand cases of retinoblastomas each year. It includes a programm for early diagnosis, training of oncopediatrician, ophtalmologists and pathologists who come to stay in Curie Institute, training for prosthesis making and financial support for medical equipment and drugs (through the GFAOP). It also implies common treatment protocol and precise registry of all cases in a common data base. This program was supportde by Sanofi Espoir, Retinostop, Curie Institute and now by a swiss foundation. It is implementing in francophone and some anglophone sub Saharan African countries. Some of the centers who have the largest number of children will finally become themselves training centers for other countries.

Conflict of interest disclosure: none

Angela Di Giannatale1
Galardi, Angela1; Colletti, Marta1; Lavarello, Chiara2; DiPaolo, Virginia1; Mascio, Paolo1; Russo, Ida1; Cozza, Raffaele1; Romanzo, Antonino3; Valente, Paola3; De Vito, Rita4; Pascucci, Luisa5; Peinado, , Hector6; Montero Carcaboso, Angel7; Munier, Francis8; Petretto, Andrea2; Locatelli, Franco1; Di Giannatale, Angela1
1. Department of Pediatric Hematology/Oncology, Bambino Gesù Children’s Hospital, IRCCS, Rome, Italy.
2. Core Facilities-Proteomics Laboratory, IRCCS Istituto Giannina Gaslini, Genoa, Italy.
3. Ophtalmology Unit, Bambino Gesù Children’s Hospital, IRCCS, Rome, Italy.
4. Department of Pathology, Bambino Gesù Children’s Hospital, IRCCS, Rome, Italy.
5. Department of Veterinary Medicine, University of Perugia, Perugia, Italy.
6. Microenvironment & Metastasis Group, Molecular Oncology Program, Spanish National Cancer Research Centre (CNIO), Madrid, Spain.
7. Institut de Recerca Sant Joan de Deu, Barcelona, Spain
8. Hopital Ophtalmique Jules Gonin – Fondation Asile des aveugles, Lausanne, Switzerland

Purpose: Retinoblastoma represents the most common intraocular malignancy of infancy and childhood. Although several tumor biomarkers have been evaluated in RB, new prognostic biomarkers, therapeutic targets and new candidates that are predictive for response to therapy are needed. In the majority of pediatric cancers, invasive techniques are necessary to validate the mutational status and/or determine the activation of specific pathways. Nevertheless, in RB the biopsy of the primary tumor is not feasible because of the risk of tumor intraocular dissemination. Tumor release molecular information into the circulation through nucleic acids, proteins, and tumor-derived extracellular vesicles that circulate in biologic fluids such as plasma and cerebrospinal fluid (CSF). In particular, exosomes, nanosized vesicles released from various cells, have been described to contain many molecules representative of the primary tumor.

Methods: Proteins and peptides are promising biomarkers since they are functionally involved in biological processes and their expression levels variate in different tumors. In our studies we performed proteomic analysis of biological liquid derived from RB patients (humor aqueous, plasma and CSF). Furthermore, we isolated exosomes released from retinoblastoma cells lines and evaluated protein content.

Results: We identified proteins involved in specific cellular process such as cellular adhesion, metabolic processes, neuronal development and vesicular trafficking. The evaluation of different timepoints showed how the treatment modify the protein content in biological fluids of these patients.

Conclusions/Significance: Our innovative approach could be used as a non-invasive method, in alternative to tissue biopsies. The liquid biopsy may facilitate the definition of prognostic subgroups through the identification of diagnostic, prognostic and/or predictive biomarkers to guide patient management.

Conflict of interest disclosure: none

Trevor Cole
West Midlands Regional Genetics Service, Birmingham Women’s and Children’s NHS Foundation Trust, Birmingham UK (BWCNHSFT) and Birmingham Health Partners and on behalf of the Birmingham National Retinoblastoma Service and the West Midlands Regional Genetics Laboratory (BWCNHSFT)

Forty percent of all cases of Retinoblastoma have a germline mutation and are at very high risk of bilateral disease, second non-ocular cancers, and induction of second cancers secondary to radiotherapy and may be in families associated with a significant risk of with further affected first degree relatives (siblings and offspring). 60 % of cases are not inherited and two somatic RB1 gene mutations occur after conception and are at low risk of bilateral disease, non-ocular second tumours and having affected first degree relatives. Definitive proof that both RB1 gene mutations are somatic requires a source of tumour DNA for analysis. With newer chemotherapeutic regimes and local treatment enucleation for unilateral retinoblastoma has decreased by approximately 50% in our practice, which would have prevented obtaining definitive somatic results. We have now shown that informative molecular results can be obtained from cell free DNA (cfDNA) obtained from anterior chamber aqueous fluid. This cfDNA can also be utilised for real time monitoring of additional somatic events and with the potential alignment of these findings with the clinical behaviour and improving prognostication and future management decisions. Furthermore we would propose that investigation of the cerebrospinal fluid, another source of cfDNA from a fluid present in a “protected compartment”, could be utilised to assess and monitor possible CNS disease. In addition we have now reported 6 cases in the West Midlands where pre-natal cfDNA testing (undertaken on a standard maternal sample in mid-trimester) has provided a validated non-invasive predictive answer long before delivery. This has significant benefits in the quality of family care and in service delivery planning, which we suggest, outweighs any short term laboratory costs.

Conflict of interest disclosure: none

Brenda Gallie
Hospital For Sick Children, Toronto, ON, Canada

Purpose: To describe innovative therapies with potential to improve care for intraocular retinoblastoma.

Methods: We describe two innovative “disruptive” technologies to reduce duration and intensity of toxic therapies to save eyes with advanced intraocular retinoblastoma for evaluation in clinical trials: vitrectomy/resection (PPV) of active tumor and delivery of chemotherapy via an episcleral device (Chemoplaque).

Results: Since 2013, PPV for residual active tumor or recurrent tumor after primary chemotherapy (IV or IAC) was performed with procedures to enhance safety on 489 eyes of 454 children. Retinoblastoma-specific mortality was 4% (2% related to PPV eye); 2% of patients are lost-to-follow-up; salvaged were 87% of eyes (minimum 2-year follow-up). Health Canada authorized compassionate “First in Human” use of the FDA-approved Chemoplaque (0.6 mg topotecan, glued to sclera) for two patients with refractory retinoblastoma in their only remaining eye. No ocular or systemic toxicity was observed. All 30+ small distributed tumors of Patient One disappeared within 28 days (complete remission, CR); the large primary calcified tumor regressed but recurred; standard therapies attained CR at one year. Patient Two had very resistant tumors to all standard therapies including external beam radiation; initial apparent complete regression of intra-retinal and vitreous disease at day 130 was followed by recurrence for which enucleation was performed to reduce risk to life; pathology was pT1.

Conclusions/Significance: Prospective clinical trials are necessary for both PPV and the Chemoplaque to establish their role in control of advanced intraocular retinoblastoma and reduce the duration and number of invasive therapies needed to save eyes.

Conflict of interest disclosure: none

Sameh Soliman
Hospital For Sick Children, Toronto, ON, Canada

Purpose: To describe optimizing techniques of laser photocoagulation in retinoblastoma utilizing optical coherence tomography (OCT) guidance.

Methods: OCT scanning of the intended treatment area was performed during examination under anesthesia. Embedded OCT software tools (calipers on variable frames) were studied in multiple cube scans (vertical and horizontal) and plotted on the red-free image to determine both extent and relevant measurements. Red-free images were compared to colored fundus photos for localizing anatomical landmarks (vessels, vessel branching, fovea or optic disc).

Results: in perifoveal tumors, laser Photocoagulation avoids the foveal center and perifoveal area by starting from crescent-shaped anti-foveal edge including outer tumor boundary with the adjacent retina and moving closer to the fovea in subsequent sessions. In invisible and subclinical tumors, calipers determine tumor location and anatomical landmarks proposed the location on the fundus photo and a single laser (532 nm) burn was fired in that proposed location. OCT showed tumor-laser burn relation and laser treatment was continued accordingly. A post-laser OCT ensured complete tumor treatment. A similar technique was utilized in tumor scar recurrences.

Conclusions: OCT guided photocoagulation can optimize visual outcome by reducing scar size, preventing surface traction and migration and avoiding foveal center.

Conflict of interest disclosure: none

Lesley Everett1
Damato, Bertil2; Afshar, Armin1
1. University Of California, San Francisco, CA, USA
2. University Of Oxford, Oxford, UK

Purpose: To determine (1) how UCSF retinoblastoma ocular salvage rates have changed since the implementation of intra-vitreal and intra-arterial chemotherapy, (2) treatment needed to achieve remission for each ICRB group, and (3) visual acuity post-treatment.

Methods: Retrospective review of 70 patients treated since 2013. Remission is defined as no recurrence for =3 months since last treatment.

Results: 100 eyes of 70 patients (43% bilateral disease) were included. RB1 germline status was negative, positive, or mosaic in 50%, 46%, and 4% of patients, respectively. The number of eyes in each ICRB Group (A-E) and the ocular salvage rates at a mean of 28 months were: A (n=14, 100%), B (n=18, 100%), C (n=9, 78%), D (n=26, 62%), and E (n=33, 12%). Relative to UCSF historic rates (1990-2012), salvage rates improved for Group D (44% vs. 8%, chi-squared test, p=2.4 x10-12) and Group E eyes (9% vs. 6%, p=0.00014). Figure-1 summarizes the type and number of treatments administered for eyes in remission for each ICRB Group, highlighting efficacy of intra-arterial chemotherapy in advanced disease. This information was used to develop a standardized retinoblastoma treatment protocol at UCSF. Most Group A-C eyes in remission retained excellent visual acuity (20/20-20/60), though some with macular tumors had acuity ranging from 20/200 to light perception. Three Group D eyes achieved acuity better than 20/700, but the remainder of Group D and E eyes in remission had poor acuity (hand-motion or counting-fingers).

Conclusions: UCSF retinoblastoma ocular salvage significantly improved with intra-vitreal and intra-arterial chemotherapy.

Conflict of interest disclosure: none

Marcus De Jong1
Kors, Wijnanda1; Moll, Annette1; De Graaf, Pim1; Castelijns, Jonas1; Jansen, Robin1; Gallie, Brenda2; Soliman, Sameh2; Shaikh, Furqan3; Dimaras, Helen2; Kivela, Tero4
1. Amsterdam UMC, Location VUMC, Amsterdam, Netherlands
2. Hospital For Sick Children, Toronto, ON, Canada
3. University Of Toronto, Toronto, ON, Canada
4. Helsinki University Central Hospital, Helsinki, Finland

Purpose: Objectives of this study were to determine until what age children are at risk for pineoblastoma, whether the onset of pineoblastoma is linked to the age at which eye tumors develop and the lead time between a detectable tumor and symptoms. Up to 4% of patients with retinoblastoma are at risk for pineal trilateral retinoblastoma (pineoblastoma). Early detection and proper treatment is essential for survival. Current evidence is unclear on the usefulness of screening for pineoblastoma and, if so, until what age.

Methods: We conducted the study according to the MOOSE guideline for reporting meta-analyses of observational studies. We searched PubMed (Medline) and Embase between January 1, 1966 and February 27, 2019 for published literature. Inclusion of all articles was performed separately and independently by two authors. Articles reporting patients with trilateral retinoblastoma with last known survival status and follow-up data were considered. Two authors independently each extracted the data from all included articles. Discrepancies were resolved in consensus. The Mann-Whitney U test was used to compare subgroups. Pearson’s r was used to calculate a correlation between two continuous variables.

Results: In total 138 pineoblastoma patients were included in the analysis. Ninety-five percent of patients with asymptomatic pineoblastoma (21/22) were diagnosed before 40 months (median 16 months, IQR 9–29). Age at pineoblastoma diagnosis was independent of age at intraocular retinoblastoma diagnosis (testing for dependency: P > 0.4). The lead time between asymptomatic and symptomatic pineoblastoma was ~1 year. From this, we calculated that for a screening program with 1 MRI scan every 6 months after retinoblastoma diagnosis (~6 months of age) until the age of 3 years, at least 311 scans would be required to detect 1 pineoblastoma.

Conclusion: This study suggests that retinoblastoma patients are at risk for pineoblastoma within a narrower time period than previously assumed and the age of retinoblastoma diagnosis, laterality and previous treatment have no influence on the age of pineoblastoma diagnosis. Screening would require numerous MRI scans to diagnose 1 pineoblastoma and even more to save 1 life, but does seem to be cost-effective.

Conflict of interest disclosure: none

Jaclyn White
Gole, Glen
Queensland Children’s Hospital, Brisbane, QLD, Australia

Purpose: Early diagnosis of retinoblastoma is essential for patient survival and the preservation of sight. The ability of parents and primary healthcare practitioners to recognise common presenting signs and symptoms is crucial in minimising time to diagnosis.

Methods: Over a period of 11 years (2008-2019), the parents of 37 patients diagnosed and treated for retinoblastoma in Queensland were interviewed and asked a series of standard questions which focussed on their child’s referral pathway. Particular attention was paid to the ‘diagnostic lag period’, the time from when signs or symptoms were first detected by a parent, to when a definitive diagnosis of retinoblastoma was made by an experienced consultant ophthalmologist. The number and type of healthcare professionals consulted prior to diagnosis was also noted.

Results: The most common presenting symptom was leukocoria (54%), followed by strabismus (27%), suspected poor vision (including apparent inability to fix and follow, and nystagmus) (11%) and heterochromia iridis (5%). One child was diagnosed antenatally on account of a positive family history. The average ‘parental lag period’ (time from when the child was first noticed to be symptomatic to when advice from primary healthcare professional (PHP) was sought) was 3.58 months (Range = 0-18 months). The average ‘practitioner lag period’ (time from primary care consultation to definitive diagnosis by a consultant ophthalmologist) was 3.55 weeks (Range = 0-9 months). In 70% of cases, general practitioners were the first PHPs consulted. In only 13 of the 37 (35%) cases was an urgent referral to an ophthalmology service issued at the initial consultation. In 10 cases, 2 or more primary care consultations were needed to secure an urgent ophthalmic referral.

Conclusion: Parents and primary care practitioners require greater education about the presenting signs and symptoms of retinoblastoma.

References: Goddard A, Kingston J et al. Delay in diagnosis of retinoblastoma: risk factors and treatment outcome. BJO 1999; 83: 1320-1323.

Conflict of interest disclosure: none

Stephen Russell1
Drack, Arlene1; Sohn, Elliott2; Han, Ian2; Stone, Edwin2
1. University Of Iowa, Department Of Ophthalmology And Visual Sciences, Iowa City, IA, USA
2. University Of Iowa, Dept Of Ophthalmology And Visual Sciences, Institute For Vision Research, Iowa City, IA, USA

Purpose: To present and discuss several post-FDA surgical interventions involving voretigene neparvovec and discuss related study cohort outcomes

Methods: Pre-, intra- and post-operative findings in selected patients that have received voretigene neparvovec for biallelic RPE65-mutation associated Leber’s Congenital Amaurosis (LCA) will be presented and discussed that illustrate non-trial related surgical or evaluation challenges.

Results: Subjects will include bleb-related retinal detachment and repair, pre-operative evaluation of full-field light sensitivity (FST) -incapable patients, FST deterioration following injection and use of intraoperative ocular coherence tomography (OCT).

Conclusions: Surgical evaluation and management of biallelic RPE65-mutation associated LCA patients post-FDA and EMA approval requires a more comprehensive clinical approach than was needed within the phase 3 trial. Complications and side effects not observed in the phase 1 and 3 voretigene neparvovec studies have been observed. With additional US and European treatments, more diverse surgical and geographic experiences will provide broader safety and efficacy profiles.

Conflict of interest disclosure: The following conflict(s) of interest must be disclosed:
Stephen R. Russel
– received grants or research support from Spark Therapeutics, Inc. and ProQR Therapeutics N.V.
– received honorary or consultation fees from Novartis Pharmaceuticals Corporation
– is stock shareholder of IDx Technologies Inc.