Ophthalmology Commons^™

Narrative Review-Drug Delivery In Age-Related Macular Degeneration, Rachel Israilevich, Raziyeh Mahmoudzadeh, Mirataollah Salabati, David Xu

Wills Eye Hospital Papers

This narrative review highlights routes of ocular drug delivery for age-related macular degeneration (AMD). AMD is the leading cause of irreversible blindness in industrialized countries and accounts for 8.7% of blindness worldwide. Advanced AMD can be classified into two subtypes: late-stage dry AMD [known as geographic atrophy (GA)] and neovascular AMD (nAMD). GA is often bilateral and results from progressive and irreversible loss of photoreceptors and areas of the retinal pigment epithelium. Wet AMD is characterized by angiogenesis from the choroid to the normally avascular regions underneath the retinal pigment epithelium (RPE) or retina, a process known as choroidal neovascularization …

Cell-Based Therapies For Retinal Diseases: A Review Of Clinical Trials And Direct To Consumer "Cell Therapy" Clinics, John Hinkle, Raziyeh Mahmoudzadeh, Ajay E. Kuriyan

Wills Eye Hospital Papers

Background: The retinal pigment epithelium (RPE) is implicated in the pathophysiology of many retinal degenerative diseases. This cell layer is also an ideal target for cell-based therapies. Several early phase clinical trials evaluating cell therapy approaches for diseases involving the RPE, such as age-related macular degeneration and Stargardt's macular dystrophy have been published. However, there have also been numerous reports of complications from unproven "cell therapy" treatments marketed by "cell therapy" clinics. This review aims to outline the particular approaches in the different published clinical trials for cell-based therapies for retinal diseases. Additionally, the controversies surrounding experimental treatments offered outside …

Conditional Analysis On New Tumor Formation With Solitary Unilateral Retinoblastoma In 482 Consecutive Patients, Carol L Shields, Philip W Dockery, Megan Ruben, Madalyne A Sunday, Martin Calotti, Antonio Yaghy

Wills Eye Hospital Papers

PURPOSE: The objective of the study was to understand dynamic risk (conditional analysis based on patient age) for new tumor development in patients with solitary unilateral retinoblastoma.

METHODS: This was a retrospective analysis.

RESULTS: Of 482 patients with solitary unilateral retinoblastoma, 55 new tumors developed in 20 patients (4%). Comparison (new tumor vs. no new tumor development) revealed those with new tumor demonstrated younger mean age at presentation (10 vs. 36 months,

CONCLUSION: Children (≤24 months) with solitary unilateral retinoblastoma showed decreasing risk for new tumors up to 24 months of life. Later onset of new tumor was more likely …

Assessing The Accuracy, Quality, And Readability Of Patient Accessible Online Resources Regarding Ocular Gene Therapy And Voretigene Neparvovec., Swetha Davuluri, Nicolas A. Yannuzzi, Amy Kloosterboer, Ajay E. Kuriyan, Jayanth Sridhar

Wills Eye Hospital Papers

Purpose: To evaluate the accuracy, quality, and readability of online information regarding the Food and Drug Administration (FDA) approved ocular gene therapy voretigene neparvovec (Luxturna, Spark Therapeutics, Philadelphia, PA, USA).

Methods: Ten online resources about voretigene neparvovec were assessed in this cross-sectional study. A novel 25-question assessment was created to evaluate the information most relevant to patients. Each article was assessed by independent graders using the assessment and the DISCERN instrument. An online readability tool, Readable, was used to assess readability. Accountability was evaluated using the Journal of the American Medical Association (JAMA) benchmarks.

Results: The average questionnaire score for …

Istent Versus Istent Inject Implantation Combined With Phacoemulsification In Open Angle Glaucoma., Wesam Shamseldin Shalaby, Sophia S. Lam, Amirmohsen Arbabi, Jonathan S. Myers, Marlene R. Moster, Natasha N. Kolomeyer, Reza Razeghinejad, Aakriti Garg Shukla, Tarek R. Hussein, Tarek M. Eid, Said M. Shalaby, Daniel Lee

Wills Eye Hospital Papers

Purpose: To compare the outcomes of iStent vs. iStent inject implantation combined with phacoemulsification.

Methods: This single center retrospective comparative case series included subjects with open angle glaucoma who underwent iStent or iStent inject implantation combined with phacoemulsification with ≥1 year follow-up. The main outcome measures were in-group and between-group changes in intraocular pressure (IOP) and medication number, proportion of eyes that achieved IOP ≤15 mmHg, and surgical success defined as 20% IOP reduction from baseline at 6/12 months. Univariate/multivariate regression analyses were done to identify predictors of surgical failure.

Results: One hundred ninety-seven eyes of 148 patients were included …

Cross-Sectional Analysis Of Baseline Visual Parameters In Subjects Recruited Into The Rescue And Reverse Nd4-Lhon Gene Therapy Studies, Mark Moster, Robert C Sergott, Nancy J Newman, Patrick Yu-Wai-Man, Valerio Carelli, Molly Scannell Bryan, Gerard Smits, Valérie Biousse, Catherine Vignal-Clermont, Thomas Klopstock, Alfredo A Sadun, Adam A. Debusk, Michele Carbonelli, Rabih Hage, Siegfried Priglinger, Rustum Karanjia, Laure Blouin, Magali Taiel, Barrett Katz, José Alain Sahel

Wills Eye Hospital Papers

OBJECTIVE: This report presents a cross-sectional analysis of the baseline characteristics of subjects with Leber hereditary optic neuropathy enrolled in the gene therapy trials RESCUE and REVERSE, to illustrate the evolution of visual parameters over the first year after vision loss.

METHODS: RESCUE and REVERSE were 2 phase III clinical trials designed to assess the efficacy of rAAV2/2-ND4 gene therapy in ND4-LHON subjects. At enrollment, subjects had vision loss for ≤6 months in RESCUE, and between 6 and 12 months in REVERSE. Functional visual parameters (best-corrected visual acuity [BCVA], contrast sensitivity [CS], and Humphrey Visual Field [HVF]) and structural parameters …

Long-Term Follow-Up After Unilateral Intravitreal Gene Therapy For Leber Hereditary Optic Neuropathy: The Restore Study, Valérie Biousse, Nancy J Newman, Patrick Yu-Wai-Man, Valerio Carelli, Mark Moster, Catherine Vignal-Clermont, Thomas Klopstock, Alfredo A Sadun, Robert C Sergott, Rabih Hage, Simona Esposti, Chiara La Morgia, Claudia Priglinger, Rustum Karanja, Laure Blouin, Magali Taiel, José-Alain Sahel

Wills Eye Hospital Papers

BACKGROUND: RESCUE and REVERSE were 2 Phase 3 clinical trials that assessed the efficacy and safety of intravitreal gene therapy with lenadogene nolparvovec (rAAV2/2-ND4) for the treatment of Leber hereditary optic neuropathy (LHON). RESTORE is the long-term follow-up study of subjects treated in the RESCUE and REVERSE trials.

METHODS: In RESCUE and REVERSE, 76 subjects with LHON because of the m.11778 G>A mutation in the mitochondrial gene ND4 received a single unilateral intravitreal injection of lenadogene nolparvovec. After 96 weeks, 61 subjects were enrolled in the long-term follow-up study RESTORE. The best-corrected visual acuity (BCVA) was assessed over a …

Intravitreal Dexamethasone Implants For Refractory Macular Edema In Eyes With Noninfectious Uveitis., Eugene Yu-Chuan Kang, Sunir Garg, Hsi-Fu Chen, Wei-Chi Wu, Linda Yi-Hsing Chen, Hung-Da Chou, Laura Liu, Kuan-Jen Chen, Yih-Shiou Hwang

Wills Eye Hospital Papers

Macular edema (ME) is a common cause of visual loss among eyes with uveitis, and its management can be challenging. Steroids are an effective treatment for ME, and intravitreal dexamethasone (DEX) implants provide sustained steroid release. The purpose of this study is to evaluate intravitreal DEX implant on refractory ME in eyes with noninfectious uveitis. A retrospective study including 52 eyes of 37 patients with refractory uveitic ME was conducted from January 2011 through August 2017 at Linkou Chang Gung Memorial Hospital in Taiwan. Patients' demographic characteristics were collected. In addition, clinical information, including corrected visual acuity (VA), intraocular pressure …

A Pilot Exploration Using Optical Coherence Tomography Angiography Analysis Of Capillary Vascular Density And Foveal Avascular Zone For The Diagnosis Of Uveal Melanoma, Jason Chien, Alicia Valverde-Megías, Gwo Farn Chien, Carol L Shields

Wills Eye Hospital Papers

No abstract provided.

Outcomes Of Intravenous Chemotherapy (Chemoreduction) For Retinoblastoma Based On Patient Age In 964 Eyes Of 554 Patients., Zeynep Bas, Lauren A. Dalvin, Sameeksha Tadepalli, Raksha Rao, Amish Shah, Ann M. Leahey, Carol L. Shields

Wills Eye Hospital Papers

PURPOSE: To evaluate retinoblastoma control after intravenous chemotherapy (chemoreduction) by patient age at presentation.

DESIGN: Retrospective case series.

METHODS: This study included 964 eyes of 554 patients treated with chemoreduction at Ocular Oncology Service at Wills Eye Hospital. Patients received 6 monthly cycles of standard chemoreduction. Additional therapies for tumor control were performed as needed.

RESULTS: Of 964 eyes, a comparison by age group (24 months) revealed more advanced age group with higher frequency of group E tumor (15% vs. 25% vs. 32% vs. 39%, P < 0.001). By treatment outcomes, complete tumor control was achieved with chemoreduction alone more often in less advanced age group (46% vs. 30% vs. 17% vs. 8%, P < 0.001). Additional treatment after chemoreduction was needed more often in more advanced age group with external beam radiotherapy (EBRT; 9% vs. 16% vs. 20% vs. 15%, P = 0.006) or enucleation (12% vs. 18% vs. 26% vs. 37%, P < 0.001). Over time (1994-1998 vs. 1999-2003 vs. 2004-2008 vs. 2009-2013 vs. 2014-2019), the paradigm for additional required treatment after chemoreduction shifted toward less EBRT (27% vs. 24% vs. 14% vs. 7% vs. 2%, P < 0.001) and more intra-arterial (0% vs. 0% vs. 1% vs. 25% vs. 48%, P < 0.001) and intravitreal (0% vs. 0% vs. 3% vs. 10% vs. 20%, P < 0.001) chemotherapy.

CONCLUSIONS: Chemoreduction is a safe and effective treatment method for patients with retinoblastoma, demonstrating …

Scleral Buckling For Primary Retinal Detachment: Outcomes Of Scleral Tunnels Versus Scleral Sutures., Matthew R. Starr, Edwin H. Ryan, Anthony Obeid, Claire Ryan, Xinxiao Gao, Malika L. Madhava, Sean M. Maloney, Adam Z. Adika, Krishi V. Peddada, Kareem Sioufi, Luv G. Patel, Michael J. Ammar, Nora J. Forbes, Antonio Capone, Geoffrey G. Emerson, Daniel P. Joseph, Dean Eliott, Carl Regillo, Jason Hsu, Omesh P. Gupta, Yoshihiro Yonekawa, For The Primary Retinal Detachment Outcomes Pro Study Group

Wills Eye Hospital Papers

Purpose: There are primarily two techniques for affixing the scleral buckle (SB) to the sclera in the repair of rhegmatogenous retinal detachment (RRD): scleral tunnels or scleral sutures.

Methods: This retrospective study examined all patients with primary RRD who were treated with primary SB or SB combined with vitrectomy from January 1, 2015 through December 31, 2015 across six sites. Two cohorts were examined: SB affixed using scleral sutures versus scleral tunnels. Pre- and postoperative variables were evaluated including visual acuity, anatomic success, and postoperative strabismus.

Results: The mean preoperative logMAR VA for the belt loop cohort was 1.05 ±" …

Here Comes The Sun … For Retinoblastoma, Carol L Shields, Jerry A Shields

Wills Eye Hospital Papers

No abstract provided.

Ocular Safety Of Repeated Intravitreal Injections Of Carboplatin And Digoxin: A Preclinical Study On The Healthy Rabbits., Alireza Khodabande, Fariba Ghassemi, Fahimeh Asadi Amoli, Hamid Riazi-Esfahani, Raziyeh Mahmoudzadeh, Mohammad Mehrpour, Niloufar Valipour

Wills Eye Hospital Papers

To evaluate the ocular safety of intravitreal carboplatin and digoxin injections as a new intravitreal chemotherapy option for retinoblastoma tumor vitreous seeds. Eighteen rabbits were divided randomly into three groups to receive intravitreal injection of Digoxin (6 rabbits), Carboplatin (7 rabbits), or Saline (5 rabbits). In every group, one eye randomly treated with 10 µg Digoxin in 0.1 cc or 1 µg Carboplatin or Saline, and the contralateral eye was considered as the control. All groups underwent three consecutive injections of the drugs with 1-week intervals. Baseline electroretinography (ERG) was recorded from both eyes of all the animals prior to …

Ten-Year Outcomes Of Uveal Melanoma Based On The Cancer Genome Atlas (Tcga) Classification In 1001 Cases., Carol L Shields, Eileen Mayro, Zeynep Bas, Philip W Dockery, Antonio Yaghy, Sara E. Lally, Arupa Ganguly, Jerry A Shields

Wills Eye Hospital Papers

Purpose: To understand the prognostic value of The Cancer Genome Atlas (TCGA) for uveal melanoma metastasis, using a simplified 4-category classification, based on tumor DNA.

Methods: A retrospective cohort study of 1001 eyes with uveal melanoma at a single center, categorized according to TCGA as Group A, B, C, or D (by fine-needle aspiration biopsy for DNA analysis), and treated with standard methods, was studied for melanoma-related metastasis at 5 and 10 years.

Results: Of 1001 eyes with uveal melanoma, the TCGA categories included Group A (n = 486, 49%), B (n = 141, 14%), C (n = 260, 26%), …

The Effect Of Ametropia On Glaucomatous Visual Field Loss., Eun Young Choi, Raymond C.S. Wong, Thuzar Thein, Louis R. Pasquale, Lucy Q. Shen, Mengyu Wang, Dian Li, Qingying Jin, Hui Wang, Neda Baniasadi, Michael V. Boland, Siamak Yousefi, Sarah R. Wellik, Carlos G. De Moraes, Jonathan S. Myers, Peter J. Bex, Tobias Elze

Wills Eye Hospital Papers

Myopia has been discussed as a risk factor for glaucoma. In this study, we characterized the relationship between ametropia and patterns of visual field (VF) loss in glaucoma. Reliable automated VFs (SITA Standard 24-2) of 120,019 eyes from 70,495 patients were selected from five academic institutions. The pattern deviation (PD) at each VF location was modeled by linear regression with ametropia (defined as spherical equivalent (SE) starting from extreme high myopia), mean deviation (MD), and their interaction (SE × MD) as regressors. Myopia was associated with decreased PD at the paracentral and temporal VF locations, whereas hyperopia was associated with …

Intravitreal Gene Therapy Vs. Natural History In Patients With Leber Hereditary Optic Neuropathy Carrying The M.11778g>A Nd4 Mutation: Systematic Review And Indirect Comparison, Nancy J. Newman, Patrick Yu-Wai-Man, Valerio Carelli, Valerie Biousse, Mark Moster, Catherine Vignal-Clermont, Robert C. Sergott, Thomas Klopstock, Alfredo A. Sadun, Jean-François Girmens, Chiara La Morgia, Adam A. Debusk, Neringa Jurkute, Claudia Priglinger, Rustum Karanjia, Constant Josse, Julie Salzmann, François Montestruc, Michel Roux, Magali Taiel, José-Alain Sahel

Wills Eye Hospital Papers

Objective: This work aimed to compare the evolution of visual outcomes in Leber hereditary optic neuropathy (LHON) patients treated with intravitreal gene therapy to the spontaneous evolution in prior natural history (NH) studies.

Design: A combined analysis of two phase three randomized, double-masked, sham-controlled studies (REVERSE and RESCUE) and their joint long-term extension trial (CLIN06) evaluated the efficacy of rAAV2/2-ND4 vs. 11 pooled NH studies used as an external control.

Subjects: The LHON subjects carried the m.11778G>A ND4 mutation and were aged ≥15 years at onset of vision loss.

Methods: A total of 76 subjects received a single …

Sociodemographic And Economic Factors In Outcomes Of Tube Shunts For Neovascular Glaucoma, Wesam S Shalaby, Amirmohsen Arbabi, Jonathan S Myers, Marlene R Moster, Reza Razeghinejad, L Jay Katz, Aakriti G Shukla

Wills Eye Hospital Papers

Importance: Few studies have analyzed associations between sociodemographic factors and neovascular glaucoma (NVG) outcomes.

Aim and background: To determine the potential impact of sociodemographic and economic factors on the NVG tube shunt surgery outcomes.

Design: Retrospective, single-center, comparative case series.

Participants: Consecutive patients who underwent tube shunt surgery for NVG and had ≥6 months of follow-up.

Materials and methods: Regional average adjusted gross income (AGI) was determined by cross-referencing self-reported residential zip codes with average AGI per zip code supplied by the Internal Revenue Service. Two groups were created: (1) lower-income: individuals from neighborhoods with the lowest 10% of AGI …

Anterior Chamber Characteristics, Endothelial Parameters, And Corneal Densitometry After Descemet Stripping Automated Endothelial Keratoplasty In Patients With Fuchs Dystrophy., Remzi Karadag, Kristin Hammersmith, Parveen Nagra, Christopher J Rapuano

Wills Eye Hospital Papers

Purpose: To compare anterior segment parameters in patients with Fuchs endothelial dystrophy (FED) who underwent Descemet stripping automated endothelial keratoplasty (DSAEK) in one eye and no corneal surgery in the fellow eye.

Methods: This prospective study was conducted on 28 eyes of 14 patients with FED who underwent DSAEK in one eye at least one year prior (DSAEK group) and no corneal surgery in the fellow eye (control group). Each eye was analyzed with the anterior segment optical coherence tomography, specular microscopy, and Scheimpflug imaging systems. Data were compared between the two groups.

Results: The mean age of the patients …

The Influence Of Axial Myopia On Optic Disc Characteristics Of Glaucoma Eyes., Jasmin Rezapour, Christopher Bowd, Jade Dohleman, Akram Belghith, James A Proudfoot, Mark Christopher, Leslie Hyman, Jost B Jonas, Massimo A Fazio, Robert N Weinreb, Linda M Zangwill

Wills Eye Hospital Papers

This study characterizes differences in glaucomatous eyes with and without high axial myopia using custom automated analysis of OCT images. 452 eyes of 277 glaucoma patients were stratified into non (n = 145 eyes), mild (n = 214 eyes), and high axial myopia (axial length (AL) > 26 mm, n = 93 eyes). Optic disc ovality index, tilt and rotation angle of Bruch´s membrane opening (BMO) and peripapillary choroidal thickness (PCT) were calculated using automated and deep learning strategies. High myopic optic discs were more oval and had larger BMO tilt than mild and non-myopic discs (both p < 0.001). Mean PCT was thinnest in high myopic eyes followed by mild and non-myopic eyes (p < 0.001). BMO rotation angle, global retinal nerve fiber layer (RNFL) thickness and BMO-minimum rim width (MRW) were similar among groups. Temporal RNFL was thicker and supranasal BMO-MRW was thinner in high myopic eyes. BMO tilt and PCT showed moderate and temporal RNFL and nasal BMO-MRW showed weak but significant associations with AL in multivariable analyses (all p < 0.05). Large BMO tilt angle and thin PCT are characteristics of highly myopic discs and were not associated with severity of glaucoma. Caution should be exercised when using sectoral BMO-MRW and RNFL thickness for glaucoma management decisions in myopic eyes.

Safety And Improved Efficacy Signals Following Gene Therapy In Childhood Blindness Caused By Gucy2d Mutations, Samuel G. Jacobson, Artur V. Cideciyan, Allen Ho, Igor V. Peshenko, Alexandra V. Garafalo, Alejandro J. Roman, Alexander Sumaroka, Vivian Wu, Arun Krishnan, Rebecca Sheplock, Sanford Boye, Alexander Dizhoor, Shannon Boye

Wills Eye Hospital Papers

A first-in-human clinical trial of gene therapy in Leber congenital amaurosis due to mutations in the GUCY2D gene is underway, and early results are summarized. A recombinant adeno-associated virus serotype 5 (rAAV5) vector carrying the human GUCY2D gene was delivered by subretinal injection to one eye in three adult patients with severe visual loss, nystagmus, but preserved retinal structure. Safety and efficacy parameters were monitored for 9 months post-operatively. No systemic toxicity was detected; there were no serious adverse events, and ocular adverse events resolved. P1 and P2 showed statistically significant rod photoreceptor vision improvement by full-field stimulus testing in …

Umbilical Amnion And Amniotic Membrane Transplantation For Infectious Scleritis And Scleral Melt: A Case Series., Zeba Syed, Christopher J Rapuano

Wills Eye Hospital Papers

Purpose: To report the outcomes of two cases of infectious scleritis with severe scleral thinning managed using combined mechanical debridement, cryopreserved umbilical amnion (UA) and amniotic membrane (AM) grafts, and antimicrobial therapy.

Observations: Two patients presented with severe infectious scleritis with progressive scleral melts secondary to Pseudomonas aeruginosa subsequent to pterygium surgery and intravitreal injection, respectively. Surgical debridement was followed by UA grafting, AM transplantation, and antimicrobial therapy. Epithelialization and vascularization were seen within 1–4 weeks post-operatively. At last follow up of 5–6 months, the structural integrity of the sclera remained preserved with no infection recurrence, graft necrosis, or wound …

White Paper On Ophthalmic Imaging For Choroidal Nevus Identification And Transformation Into Melanoma, Carol Shields, Sara E. Lally, Lauren Dalvin, Mandeep Sagoo, Marco Pellegrini, Swathi Kaliki, Ahmet Kaan Gündüz, Minoru Furuta, Prithvi Mruthyunjaya, Adrian T. Fung, Jay S. Duker, Sara M. Selig, Antonio Yaghy, Sandor R. Ferenczy, Malvina B. Eydelman, Mark S. Blumenkranz

Wills Eye Hospital Papers

Purpose: To discuss the evolution of noninvasive diagnostic methods in the identification of choroidal nevus and determination of risk factors for malignant transformation as well as introduce the novel role that artificial intelligence (AI) can play in the diagnostic process. Methods: White paper. Results: Longstanding diagnostic methods to stratify benign choroidal nevus from choroidal melanoma and to further determine the risk for nevus transformation into melanoma have been dependent on recognition of key clinical features by ophthalmic examination. These risk factors have been derived from multiple large cohort research studies over the past several decades and have garnered widespread use …

A Systematic Review On Three Major Types Of Scleral-Fixated Intraocular Lens Implantation, Ho Ming Wong, Ka Wai Kam, Christopher J Rapuano, Alvin L Young

Wills Eye Hospital Papers

PURPOSE: We performed a systematic review on 3 major types of scleral-fixated intraocular lens (SFIOL) implantations and conducted subgroup analyses on pediatric population and subjects with Marfan syndrome.

DESIGN: Systematic review.

METHODS: We performed a search in PubMed, Ovid MEDLINE, and Embase for English language articles with keywords "(sutured intraocular lens) OR (SFIOL) OR (sutureless intraocular lens) OR (glued intraocular lens) OR (intrascleral intraocular lens) OR (SFIOL)" through October 16, 2019. Articles reporting individual outcomes after SFIOL were included in this systematic review. Recorded outcome measures included intraoperative and postoperative complications, endothelial cell changes, and intraocular lens-related outcomes.

RESULTS: Our …