LEAN SIX SIGMA TECHNIQUES TO IMPROVE OPHTHALMOLOGY CLINIC EFFICIENCY.

PURPOSE: Ophthalmologists serve an increasing volume of a growing elderly population undergoing increasingly complex outpatient medical care, including extensive diagnostic testing and treatment. The resulting prolonged patient visit times ("patient flow times") limit quality, patient and employee satisfaction, and represent waste. Lean Six Sigma process improvement was used in a vitreoretinal practice to decrease patient flow time, demonstrating that this approach can yield significant improvement in health care. METHODS: Process flow maps were created to determine the most common care pathways within clinic. Three months' visits from the electronic medical record system, which tracks patient task times at each process step in the office were collected. Care tasks and care pathways consuming the greatest time and variation were identified and modified. Follow-up analysis from 6 weeks' visits was conducted to assess improvement. RESULTS: Nearly all patients took one of five paths through the office. Patient flow was redesigned to reduce waiting room time by having staff members immediately start patients into one of those five paths; staffing was adjusted to address high demand tasks, and scheduling was optimized around derived predictors of patient flow times. Follow-up analysis revealed a statistically significant decline in mean patient flow time by 18% and inpatient flow time SD by 4.6%. Patient and employee satisfaction scores improved. CONCLUSION: Manufacturing industry techniques, such as Lean and Six Sigma, can be used to improve patient care, minimize waste, and enhance patient and staff satisfaction in outpatient clinics.

Emerging vascular endothelial growth factor antagonists to treat neovascular age-related macular degeneration.

INTRODUCTION: Evolving anti-vascular endothelial growth factor (VEGF) treatments for neovascular age-related macular degeneration (nAMD) include long acting agents, combination strategies involving new pathways, topical agents, sustained-release, and genetic therapy strategies. Areas covered: Brolucizumab and abicipar pegol have smaller molecular size, facilitating higher concentrations and potentially longer duration than current anti-VEGF agents. Agents being combined with anti-VEGFs include OPT-302 (to inhibit VEGF-C and VEGF-D); pegpleranib and rinucumab (to inhibit platelet derived growth factor, PDGF - but both failed to show consistently improved visual outcomes compared to anti-VEGF monotherapy); and RG7716, ARP-1536 and nesvacumab (to activate the Tie-2 tyrosine kinase receptor, which reduces permeability). X-82 is an oral anti-VEGF and anti-PDGF being tested in phase 2 studies. Topical anti-VEGF ± anti-PDGF drugs under study include pazopanib, PAN-90806, squalamine lactate, regorafinib, and LHA510. Sustained-release anti-VEGF delivery treatments, such as the ranibizumab Port Delivery System, GB-102, NT-503, hydrogel depot, Durasert, and ENV1305 aim to reduce the burden of frequent injections. Gene therapies with new viral vectors hold the potential to induce sustained expression of anti-angiogenic proteins via the retina's cellular apparatus, and include AVA-101/201, ADVM-202/302, AAV2-sFLT01, RGX314, and Retinostat. Expert opinion: There are many emerging anti-VEGF treatments that aim to improve visual outcomes and reduce the treatment burden of nAMD.

RANIBIZUMAB FOR DIABETIC MACULAR EDEMA REFRACTORY TO MULTIPLE PRIOR TREATMENTS.

PURPOSE: Diabetic macular edema can be refractory to multiple treatment modalities. Although there have been anecdotal reports of ranibizumab showing efficacy when other modalities provided limited benefit, little has been published on treatment for refractory diabetic macular edema. This study sought to investigate this observation further. METHODS: Retrospective chart review. RESULTS: Thirty-three eyes of 22 patients with refractory diabetic macular edema were treated with 0.3 mg intravitreal ranibizumab. This group of eyes received an average of 5.1 prior treatments (macular laser, intravitreal bevacizumab, triamcinolone acetonide, or dexamethasone implant). The mean best corrected visual acuity before the initial ranibizumab injection was 20/110 and the mean central subfield thickness was 384 µm. After 7 visits over an average of 48 weeks, during which an average of 6 ranibizumab injections were administered, the mean visual acuity improved to 20/90 and the mean central subfield thickness improved to 335 µm. Both central subfield thickness and best corrected visual acuity improved with number of days of follow-up in a statistically significant fashion (P < 0.01). Similarly, both central subfield thickness and visual acuity improved with number of ranibizumab injections in a linear fashion, but this was not statistically significant. CONCLUSION: Ranibizumab can improve diabetic macular edema refractory to prior treatments of laser photocoagulation, intravitreal triamcinolone acetonide, and bevacizumab.

Sutureless scleral fixation of intraocular lenses: outcomes of two approaches. The 2014 Yasuo Tano Memorial Lecture.

PURPOSE: We sought to assess the clinical outcomes and complications of two approaches to scleral fixation of intraocular lenses (IOLs): transconjunctival fixation through trocar cannulas and fixation using scleral tunnels created with a microvitreoretinal (MVR) blade. METHODS: This retrospective chart review was comprised of 23 eyes that received scleral fixation of a three-piece IOL with concurrent pars plana vitrectomy between June 2012 and June 2014. Scleral fixation was performed either by transconjunctival fixation through trocar cannulas (cannula fixation) or by the creation of scleral tunnels using an MVR blade (tunnel fixation). The preoperative and postoperative corrected distance visual acuities (CDVA), spherical equivalents (SE), and complications were evaluated. RESULTS: 15 cannula fixations and 8 tunnel fixations were performed. Mean follow-up was 353 days (Range: 94 - 790 days). Fifteen IOLs were fixated 2 mm posterior to the limbus. Seven IOLs were fixated 1.5 mm posterior to the limbus, and one IOL was fixated 0.75 mm posterior to the limbus. Mean preoperative CDVA was logMAR 1.17 (Snellen 20/297), and mean postoperative CDVA was logMAR 0.37 (Snellen 20/47) (p <0.0001). At last follow-up, none of the IOLs have dislocated or subluxed and there has been no erosion of the subconjunctival haptics. CONCLUSIONS: Scleral fixation of IOLs using trocar cannulas or scleral tunnels is an effective surgical option for the treatment of aphakia or IOL dislocation. Both techniques result in significant visual improvement with minimal postoperative complications.

EPITHELIAL DOWNGROWTH IN THE VITREOUS CAVITY AND ON THE RETINA IN ENUCLEATED SPECIMENS AND IN EYES WITH VISUAL POTENTIAL.

PURPOSE: To report clinical course and visual and anatomical outcomes of six eyes with histopathologically confirmed vitreous cavity and retina epithelial downgrowth. METHODS: This is a retrospective 15-year review of archived pathologic slides and corresponding medical records of patients with vitreous cavity and retina epithelial downgrowth. Posterior segment epithelial downgrowth was defined as epithelial or goblet cells in the vitreous cavity or on the surface of the retina. RESULTS: Histopathologic diagnosis of epithelial downgrowth was made in 122 patients. Of those, 6 patients (5%) had vitreous cavity and retina epithelial downgrowth. Three patients developed blind painful eye, and epithelial downgrowth was identified in enucleated specimens. The other three eyes with visual potential presented with tractional retinal detachments. Epithelial downgrowth was identified in epiretinal membranes obtained during pars plana vitrectomy. The latter group had more previous surgeries (P = 0.03), and all had keratoprosthesis implantation as their last surgery. All three had pathologic specimens obtained at the time of the keratoprosthesis implantation; no anterior segment epithelial downgrowth was noted in two patients, and one patient had involvement of corneal button, iris, and posterior capsule. Final visual acuity ranged from hand motion to light perception. CONCLUSION: In the current study, vitreous cavity and retina epithelial downgrowth occurred after multiple intraocular surgeries, including repair of the open globe injuries both in enucleated specimens and in eyes with visual potential. In eyes with visual potential, keratoprosthesis implantation seems to predispose the development of posterior segment epithelial downgrowth.

Recurrent orbital adult-type fibrosarcoma in a 3-year-old girl.

A 3-year-old Filipino girl presented with progressive left-sided ptosis and proptosis after resection of a superomedial orbital tumor 2.5 years ago. She had been followed with serial MRI, which demonstrated interval growth of a recurrent lesion. Repeat resection was undertaken via an eyelid-splitting anterior orbitotomy. The patient's pediatric oncologist and sarcoma specialist did not recommend adjuvant chemotherapy, and the family declined proton radiotherapy. The patient will continue to be monitored with serial imaging. Histopathology, immunohistochemistry, and reverse transcriptase polymerase chain reaction were most consistent with a diagnosis of adult-type fibrosarcoma. This is the first reported case of adult-type fibrosarcoma presenting in the orbit of a child. Fibrosarcoma is a fibroblast-derived tumor that commonly presents in the extremities, usually in patients in their fourth to sixth decades. It is rarely seen in the orbit, with the largest case series to date only including 5 patients.

UV-independent p53 mutations in sebaceous carcinoma of the eyelid.

PURPOSE: Sebaceous carcinoma of the eyelid is a potentially fatal malignancy that has been associated with p53 gene mutations. The purpose of this study is to determine the frequency of p53 mutations in sebaceous carcinoma of the eyelid and to determine whether there is any relationship between the presence of p53 mutations and tumor invasiveness. METHODS: Retrospective case series. Fourteen samples of sebaceous carcinoma that had been resected from Caucasian patients between 1994 and 2010 were analyzed for p53 gene mutations with PCR and Sequencher software. Patient charts were reviewed to draw clinicopathologic correlations in relation with the presence of p53 gene mutations. RESULTS: Seven of 14 (50%) sebaceous carcinoma samples were found to have p53 gene mutations. None of the samples had tandem mutations, which are caused by UV exposure. No statistically significant trend was found between the presence of p53 mutations and metastasis, recurrence, tumor size, TNM stage, and pagetoid spread. There was a similar frequency of p53 gene mutations found in stage T1, T2, and T3 tumors. CONCLUSIONS: p53 Mutations are found in a high percentage of sebaceous carcinomas in the Caucasian population. The absence of tandem mutations is consistent with the belief that sebaceous carcinoma develops as a UV-independent process. There does not appear to be a significant correlation between the presence of p53 mutations and tumor size, recurrence, metastasis, pagetoid spread, or location. The similar frequency of p53 mutations in both low- and high-stage tumors implies that p53 gene mutations may be involved in early stages of carcinogenesis of sebaceous carcinoma.

Transitional cell-type papillary carcinoma of the lacrimal sac manifesting as a medial canthal skin lesion.

A 61-year-old man presented with a 2.5 cm fungating skin lesion above the right medial canthus, accompanied by fluctuance and subtle inferotemporal globe displacement. The tumor had erupted 2 months previously and grown rapidly. Computed tomography (CT) revealed a 4.2 × 2.8 × 2.1 cm exophytic mass of the right orbit, superimposed on chronic dacryocystitis. Incisional biopsy disclosed faulty epithelial maturation sequence with possible basement membrane invasion. The patient underwent wide excision with medial maxillectomy, inferior turbinectomy, ethmoidectomy, and partial rhinectomy. The orbital floor was then reconstructed; a paramedian forehead flap and myocutaneous cheek advancement flap were used to fill cutaneous defects. All surgical margins were negative on both frozen and permanent sections. Definitive histopathology was consistent with transitional cell type papillary carcinoma of the lacrimal sac. Adjuvant radiotherapy was recommended, but the patient has declined further treatment. He remains recurrence-free at one year.

Structure-guided engineering of immunotherapies targeting TRBC1 and TRBC2 in T cell malignancies.

Peripheral T cell lymphomas are typically aggressive with a poor prognosis. Unlike other hematologic malignancies, the lack of target antigens to discriminate healthy from malignant cells limits the efficacy of immunotherapeutic approaches. The T cell receptor expresses one of two highly homologous chains [T cell receptor ß-chain constant (TRBC) domains 1 and 2] in a mutually exclusive manner, making it a promising target. Here we demonstrate specificity redirection by rational design using structure-guided computational biology to generate a TRBC2-specific antibody (KFN), complementing the antibody previously described by our laboratory with unique TRBC1 specificity (Jovi-1) in targeting broader spectrum of T cell malignancies clonally expressing either of the two chains. This permits generation of paired reagents (chimeric antigen receptor-T cells) specific for TRBC1 and TRBC2, with preclinical evidence to support their efficacy in T cell malignancies.

Altered neural activation in ornithine transcarbamylase deficiency during executive cognition: an fMRI study.

BACKGROUND: Ornithine transcarbamylase deficiency (OTCD) is an X-linked urea cycle disorder characterized by hyperammonemia resulting in white matter injury and impairments in working memory and executive cognition. OBJECTIVE: To test for differences in BOLD signal activation between subjects with OTCD and healthy controls during a working memory task. DESIGN, SETTING AND PATIENTS: Nineteen subjects with OTCD and 21 healthy controls participated in a case-control, IRB-approved study at Georgetown University Medical Center. INTERVENTION: An N-back working memory task was performed in a block design using 3T functional magnetic resonance imaging. RESULTS: In subjects with OTCD we observed increased BOLD signal in the right dorsolateral prefrontal cortex (DLPFC) and anterior cingulate cortex (ACC) relative to healthy age matched controls. CONCLUSIONS: Increased neuronal activation in OTCD subjects despite equivalent task performance points to sub-optimal activation of the working memory network in these subjects, most likely reflecting damage caused by hyperammonemic events. These increases directly relate to our previous finding of reduced frontal white matter integrity in the superior extents of the corpus callosum; key hemispheric connections for these areas. Future studies using higher cognitive load are required to further characterize these effects.

Efficient clinical-grade γ-retroviral vector purification by high-speed centrifugation for CAR T cell manufacturing.

γ-Retroviral vectors (γ-RV) are powerful tools for gene therapy applications. Current clinical vectors are produced from stable producer cell lines which require minimal further downstream processing, while purification schemes for γ-RV produced by transient transfection have not been thoroughly investigated. We aimed to develop a method to purify transiently produced γ-RV for early clinical studies. Here, we report a simple one-step purification method by high-speed centrifugation for γ-RV produced by transient transfection for clinical application. High-speed centrifugation enabled the concentration of viral titers in the range of 107-108 TU/mL with >80% overall recovery. Analysis of research-grade concentrated vector revealed sufficient reduction in product- and process-related impurities. Furthermore, product characterization of clinical-grade γ-RV by BioReliance demonstrated two-logs lower impurities per transducing unit compared with regulatory authority-approved stable producer cell line vector for clinical application. In terms of CAR T cell manufacturing, clinical-grade γ-RV produced by transient transfection and purified by high-speed centrifugation was similar to γ-RV produced from a clinical-grade stable producer cell line. This method will be of value for studies using γ-RV to bridge vector supply between early- and late-stage clinical trials.

KSI-301: an investigational anti-VEGF biopolymer conjugate for retinal diseases.

INTRODUCTION: KSI-301 is an intravitreal anti-vascular endothelial growth factor (VEGF) agent in clinical trials for the treatment of neovascular age-related macular degeneration (nAMD), diabetic retinopathy, diabetic macular edema (DME), and retinal vein occlusion (RVO). Its antibody-biopolymer conjugate structure is designed to decrease clearance from the eye and increase the duration of the effect. AREAS COVERED: This article briefly discusses the impact and mechanisms of nAMD, DME, and RVO and evaluates currently approved anti-VEGF therapies. It progresses to examine a new agent, KSI-301 and the results from numerous clinical trials in these disease areas. EXPERT OPINION: Despite varied results in the phase 2b/3 study for nAMD, there is potential for KSI-301 to serve as a durable therapy for VEGF-mediated retinal disorders. Ongoing phase 3 trials for nAMD, DME, and RVO will provide additional evidence on its efficacy, duration, and safety profiles.

Longer-Term Anti-VEGF Therapy Outcomes in Neovascular Age-Related Macular Degeneration, Diabetic Macular Edema, and Vein Occlusion-Related Macular Edema: Clinical Outcomes in 130 247 Eyes.

PURPOSE: The clinical practice visual acuity (VA) outcomes of anti-VEGF therapy for up to 5 years were assessed in patients with neovascular age-related macular degeneration (nAMD), diabetic macular edema (DME), branch retinal vein occlusion-related macular edema (BRVO-ME), and central retinal vein occlusion-related macular edema (CRVO-ME). DESIGN: A retrospective analysis was performed using the Vestrum Health Retina Database. PARTICIPANTS: Treatment-naive patients with nAMD, DME, BRVO-ME, or CRVO-ME who received anti-VEGF injections between 2014 and 2019 and had follow-up data for ≥12 months. METHODS: Data on age, sex, the number of anti-VEGF treatments, and VA were analyzed. MAIN OUTCOME MEASURES: Mean VA change up to 3 years (BRVO-ME and CRVO-ME) and 5 years (nAMD and DME). RESULTS: At 1, 3, and 5 years, in 67 666, 21 305, and 5208 eyes with nAMD, after a mean of 7.6, 19.5, and 32 injections, there was a mean change of +3.1, -0.2, and -2.2 letters, respectively. At 1, 3, and 5 years, in 40 832, 7728, and 1192 eyes with DME, after a mean of 6.2, 15.4, and 26.0 injections, there was a mean change of +4.7, +3.3, and +3.1 letters, respectively. At 1 and 3 years, in 12 451 and 3027 eyes with BRVO-ME, after a mean of 7.1 and 18.2 injections, there was a mean change of +9.5 and +7.7 letters, respectively. At 1 and 3 years, in 9298 and 2264 eyes with CRVO-ME, after a mean of 7.3 and 18.8 injections, there was a mean change of +8.3 and +6.0 letters, respectively (P < 0.01 for all VA changes of > 1 letter). In all 4 conditions, the mean VA increased with the mean number of anti-VEGF injections, eyes with a baseline VA of 20/40 or better tended to lose VA, and eyes with progressively worse baseline VA experienced a progressively greater VA gain at 3 years. CONCLUSIONS: In practice, patients with nAMD, DME, BRVO-ME, and CRVO-ME showed limited visual outcomes, with patients with nAMD tending to lose VA at 3 and 5 years. Across all 4 disorders, the mean change in VA correlated with treatment intensity at 1, 3, and 5 years. Patients with better baseline VA are more vulnerable to vision loss.

Multimodal Imaging Findings in Two Children With Microphthalmos.

Microphthalmos, also called microphthalmia, is a rare developmental disorder of the eye that can be caused by genetic or chromosomal abnormalities or environmental factors. The spectrum of clinical presentation includes nanophthalmia and posterior microphthalmia. It affects approximately one in 1,000 individuals, although there is insufficient literature regarding the clinical and different imaging modalities findings. [Ophthalmic Surg Lasers Imaging Retina. 2021;52:444-446.].

Vascular Endothelial Growth Factor Antagonists: Promising Players in the Treatment of Neovascular Age-Related Macular Degeneration.

Neovascular age-related macular degeneration (nAMD) treatment has been revolutionized by the introduction of vascular endothelial growth factor antagonists (anti-VEGF), but the need for frequent intravitreal injections poses a heavy burden to patients and physicians. Evolving anti-VEGF therapies include longer duration agents, approaches that target multiple pathways, topical anti-VEGF agents, sustained-release, and genetic therapies. Abicipar pegol, a designed ankyrin repeat protein (DARPin), demonstrated the ability to maintain stable visual acuity with 12-week dosing, but was not approved by the FDA due to higher than usual rates of intraocular inflammation. Conbercept, a recombinant anti-VEGF fusion protein, has been approved in China, and is in Phase 3 trials globally. KSI-301 is an anti-VEGF antibody biopolymer conjugate that allowed 66% of nAMD patients to maintain at least a 6-month treatment-free interval in Phase 1b studies. OPT-302, an inhibitor of VEGF-C/D, will be tested in phase 3 studies that compare anti-VEGF-A monotherapy against combination therapy with OPT-302. Faricimab is a bispecific anti-VEGF/Ang-2 antibody that upregulates the Tie-2 signaling pathway and promotes vascular stability; it is undergoing phase 3 trials with potential for 12- or 16-week dosing. PAN-90806 is a topical anti-VEGF agent that showed the ability to reduce injection frequency by 79% compared to ranibizumab monotherapy in a phase 1/2a trial. Sustained-release anti-VEGF therapies include the ranibizumab Port Delivery System (in phase 3 studies), GB-102 (Phase 2b), OTX-TKI (phase 1), and Durasert (preclinical). Suprachoroidal delivery of the tyrosine kinase inhibitor, axitinib, is in preclinical studies. Genetic therapies in phase 1 studies include RGX-314 and ADVM-022, which introduce a viral vector that modifies the retina's cellular apparatus to create an anti-VEGF biofactory, potentially serving as a one-time treatment. Further investigation is warranted for drugs and delivery systems that hope to advance visual outcomes and reduce treatment burden of nAMD.

Brolucizumab for persistent macular fluid in neovascular age-related macular degeneration after prior anti-VEGF treatments.

BACKGROUND: Some patients with neovascular age-related macular degeneration (nAMD) have persistent intraretinal/subretinal fluid (IRF/SRF) despite being treated with anti-VEGF agents. There is limited data on efficacy of switching to intravitreal brolucizumab (IVBr) in these patients. PURPOSE: To determine anatomic and visual outcomes of eyes with nAMD treated with for persistent IRF/SRF. METHODS: Retrospective series of eyes with nAMD treated initially with aflibercept (IVA, n = 48) and bevacizumab (IVBe, n = 10), then switched to IVBr for persistent IRF/SRF. RESULTS: In the IVA-IVBr group, a mean of 42 days after one IVBr, mean logMAR changed from 0.50 to 0.49 (p = 0.73) and mean CSFT changed from 340 to 305 µm (p < 0.001); 31% of eyes had no fluid, 42% had persistent but reduced fluid, 25% had stable fluid, and 2% had increased fluid. For a subgroup of 25 eyes that completed a series of 3 IVBr, mean logMAR changed from 0.44 to 0.40 (p = 0.35) and mean CSFT changed from 325 to 277 µm (p = 0.001); 24% of eyes had no fluid at last follow-up, a mean of 54 days after last IVBr. In the IVBe-IVBr group, a mean of 44 days after one IVBr, mean logMAR changed from 0.46 to 0.40 (p = 0.114) and mean CSFT from 401 to 325 µm (p = 0.009); 30% of eyes had no fluid and 70% had persistent but reduced fluid. For a subgroup of four eyes that completed a series of three IVBr, mean logMAR changed from 0.33 to 0.35 (p = 0.391) and mean CSFT improved from 375 to 275 µm (p = 0.001); 50% of eyes had no fluid at last follow-up, a mean of 65 days after last IVBr. CONCLUSION: In nAMD eyes previously treated with IVA and IVBe, switching to IVBr significantly reduced persistent IRF/SRF but did not significantly affect visual outcomes.

Comparison Between Graders in Detection of Diabetic Neovascularization With Swept Source Optical Coherence Tomography Angiography and Fluorescein Angiography.

PURPOSE: We compared the ability of ophthalmologists to identify neovascularization (NV) in patients with proliferative diabetic retinopathy using swept-source optical coherence tomography angiography (SS-OCTA) and fluorescein angiography (FA). DESIGN: Retrospective study comparing diagnostic instruments. METHODS: Eyes with proliferative diabetic retinopathy or severe nonproliferative diabetic retinopathy and a high suspicion of NV based on clinical examination were imaged using SS-OCTA and FA at the same visit. Two separate grading sets consisting of scrambled, anonymized SS-OCTA and FA images were created. The ground truth for presence of NV was established by consensus of 2 graders with OCTA experience who did not participate in the subsequent assessment of NV in this study. The 2 anonymized image sets were graded for presence or absence of NV by 12 other graders that included 2 residents, 6 vitreoretinal fellows, and 4 vitreoretinal attending physicians. The percentage of correct grading of NV using SS-OCTA and FA was assessed for each grader and across grader training levels. RESULTS: Forty-seven eyes from 24 patients were included in this study. Overall, the mean percentage of correct NV grading was 87.8% using SS-OCTA with B-scans and 86.2% using FA (P = .92). Assessing each grader individually, there was no statistically significant asymmetry in correct grading using SS-OCTA and FA. CONCLUSIONS: Ophthalmologists across training levels were able to identify diabetic NV with equal accuracy using SS-OCTA and FA. Based on these results, SS-OCTA may be an appropriate standalone modality for diagnosing diabetic NV.

Voretigene Neparvovec in Retinal Diseases: A Review of the Current Clinical Evidence.

Subretinal gene therapy trials began with the discovery of RPE65 variants and their association with Leber congenital amaurosis. The RPE65 protein is critical for the normal functioning of the visual phototransduction cascade. RPE65 gene knockout animal models were developed and showed similar diseased phenotypes to their human counterparts. Proof of concept studies were carried out in these animal models using subretinal RPE65 gene replacement therapy, resulting in improvements in various visual function markers including electroretinograms, pupillary light responses, and object avoidance behaviors. Positive results in animal models led to Phase 1 human studies using adeno-associated viral vectors. Results in these initial human studies also showed positive impact on visual function and acceptable safety. A landmark Phase 3 study was then conducted by Spark Therapeutics using a dose of 1.5 x1011 vector genomes after dose-escalation studies confirmed its efficacy and safety. Multi-luminance mobility testing was used to measure the primary efficacy endpoint due to its excellent reliability in detecting the progression of inherited retinal diseases. After the study met its primary endpoint, the Food and Drug Administration approved voretigene neparvovec (Luxturna®) for use in RPE65-associated inherited retinal diseases.

Complex Combined Tractional and Rhegmatogenous Retinal Detachment in a Twenty-Three-Year-Old Male With Wagner Syndrome.

Wagner syndrome is a rare hereditary vitreoretinopathy that has been reported in only about 300 people worldwide. It is caused by a mutation in the VCAN gene that encodes for the proteoglycan versican, which is a major component of the extracellular matrix of the vitreous gel; retinal detachment is uncommon in these cases. The authors report a case of a 23-year-old male who presented with bilateral combined tractional and rhegmatogenous retinal detachments. [Ophthalmic Surg Lasers Imaging Retina. 2020;51:467-471.].