Cobalt is a widely used in the industrial production of hard metals. Cobalt ingestion has been re... more Cobalt is a widely used in the industrial production of hard metals. Cobalt ingestion has been reported to cause widespread systemic toxicity, but its effects on vision have been sparsely reported. The authors report the case of a patient who ingested cattle magnets, which remained in his stomach for an unknown duration of time. These magnets largely consist of cobalt that gradually leached into his blood stream, resulting in protean systemic manifestations, which included optic atrophy.
Objective-To determine safety and efficacy of subretinal gene therapy in the RPE65 form of Leber ... more Objective-To determine safety and efficacy of subretinal gene therapy in the RPE65 form of Leber congenital amaurosis using recombinant adeno-associated virus 2 (rAAV2) carrying human RPE65 gene.
Purpose: To evaluate the safety and efficacy of a dexamethasone sustained-release intracanalicula... more Purpose: To evaluate the safety and efficacy of a dexamethasone sustained-release intracanalicular insert (DII) (Dextenza ® Ocular Therapeutix, Inc., Bedford, MA) for control of inflammation and pain after pars plana vitrectomy (PPV) compared to standard topical steroid therapy. Methods: Retrospective, case-matched comparison of consecutive patients undergoing PPV. Control patients were matched by diagnosis and procedure performed. The primary outcome was the proportion of patients with complete anterior chamber cell clearance (ACCC) at postoperative day 7. Secondary outcomes included proportion developing intraocular pressure (IOP) >25 mmHg, change in mean optical coherence tomography central foveal thickness (OCT CFT), and proportion developing cystoid macular edema (CME) on qualitative analysis of OCT. The DII group had a statistically significant higher rate of complete ACCC compared to the topical steroid group (65% versus 35%, respectively, with p=0.01). No eyes had IOP >25 mmHg in the DII, compared to 2 eyes in the topical steroid group (not statistically significant). Overall, mean OCT CFT decreased in both groups; one patient had CME in the DII group, as compared to three in the topical steroid group (not statistically significant). The dexamethasone intracanalicular insert provided excellent safety and efficacy in control of postoperative inflammation following PPV in this retrospective casematched study.
Mutations in the ORF15 exon of the RPGR gene cause a common form of X-linked retinitis pigmentosa... more Mutations in the ORF15 exon of the RPGR gene cause a common form of X-linked retinitis pigmentosa, which often results in severe loss of vision. In dogs and mice, gene augmentation therapy has been shown to arrest the progressive degeneration of rod and cone photoreceptors. However, the distribution of potentially treatable photoreceptors across the human retinas and the rate of degeneration are not known. Here, we have defined structural and functional features of the disease in 70 individuals with ORF15 mutations. We also correlated the features observed in patients with those of three Rpgr-mutant (Rpgr-ko, Rd9, and Rpgr-cko) mice. In patients, there was pronounced macular disease. Across the retina, rod and cone dysfunction showed a range of patterns and a spectrum of severity between individuals, but a high symmetry was observed between eyes of each individual. Genotype was not related to disease expression. In the Rpgr-ko mice, there were intraretinal differences in rhodopsin and cone opsin trafficking. In Rd9 and Rpgr-cko mice, retinal degeneration showed interocular symmetry. Longitudinal results in patients revealed localized rod and cone dysfunction with progression rates of 0.8 to 1.3 log per decade in sensitivity loss. Relatively retained rod and cone photoreceptors in mid-and far-peripheral temporal-inferior and nasal-inferior visual field regions should be good targets for future localized gene therapies in patients. †J.C. and A.V.C. contributed equally to this study.
The laboratory rat (Rattus norvegicus) is a key animal model for biomedical research. However, th... more The laboratory rat (Rattus norvegicus) is a key animal model for biomedical research. However, the genetic infrastructure required for connecting phenotype and genotype in the rat is currently incomplete. Here, we report the construction and integration of two genomic maps: a dense genetic linkage map of the rat and the first radiation hybrid (RH) map of the rat. The genetic map was constructed in two F2 intercrosses (SHRSP × BN and FHH × ACI), containing a total of 4736 simple sequence length polymorphism (SSLP) markers. Allele sizes for 4328 of the genetic markers were characterized in 48 of the most commonly used inbred strains. The RH map is a lod ≥ 3 framework map, including 983 SSLPs, thereby allowing integration with markers on various genetic maps and with markers mapped on the RH panel. Together, the maps provide an integrated reference to >3000 genes and ESTs and >8500 genetic markers (5211 of our SSLPs and >3500 SSLPs developed by other groups). [Bihoreau et al. ...
Purpose: To evaluate the safety and efficacy of a dexamethasone sustained-release intracanalicula... more Purpose: To evaluate the safety and efficacy of a dexamethasone sustained-release intracanalicular insert (DII) (Dextenza ® Ocular Therapeutix, Inc., Bedford, MA) for control of inflammation and pain after pars plana vitrectomy (PPV) compared to standard topical steroid therapy. Methods: Retrospective, case-matched comparison of consecutive patients undergoing PPV. Control patients were matched by diagnosis and procedure performed. The primary outcome was the proportion of patients with complete anterior chamber cell clearance (ACCC) at postoperative day 7. Secondary outcomes included proportion developing intraocular pressure (IOP) >25 mmHg, change in mean optical coherence tomography central foveal thickness (OCT CFT), and proportion developing cystoid macular edema (CME) on qualitative analysis of OCT. The DII group had a statistically significant higher rate of complete ACCC compared to the topical steroid group (65% versus 35%, respectively, with p=0.01). No eyes had IOP >25 mmHg in the DII, compared to 2 eyes in the topical steroid group (not statistically significant). Overall, mean OCT CFT decreased in both groups; one patient had CME in the DII group, as compared to three in the topical steroid group (not statistically significant). The dexamethasone intracanalicular insert provided excellent safety and efficacy in control of postoperative inflammation following PPV in this retrospective casematched study.
American Journal of Ophthalmology Case Reports, 2020
To describe the clinical and pathologic characteristics of a case of retinal vasculitis and vitri... more To describe the clinical and pathologic characteristics of a case of retinal vasculitis and vitritis following brolucizumab administration and subsequent ranibizumab treatment. Observations: A 76-year old Caucasian woman experienced pain, decreased vision and floaters one week after receiving her third monthly intravitreal brolucizumab injection in the right eye for exudative age-related macular degeneration. Examination was significant for 0.5+ anterior chamber cells, vitritis, mild peripheral vascular sheathing, and decreased vision from 20/70 to 20/200. She was started on topical 1% prednisolone acetate with improvement in her examination. She was switched to ranibizumab one month after her last brolucizumab injection of the right eye. Three weeks after her ranibizumab injection, she noticed photophobia, pain and decreased vision. Examination revealed worsening uveitis, vitritis, vascular sheathing, and decreased vision to count fingers. Despite starting on 0.05% difluprednate drops every 2 hours and oral high-dose methylprednisolone, the patient did not have any significant improvement in her symptoms or examination. She underwent pars plana vitrectomy and vitreous biopsy with intravitreal triamcinolone injection to the right eye. Vitreous biopsy and culture ruled out infectious endophthalmitis, and further cytopathologic analysis revealed chronic inflammatory infiltrate. Treatment with brolucizumab can result in intraocular inflammation and retinal vasculitis likely due to a delayed hypersensitivity reaction to the drug, supported by cytopathologic analysis of a vitreous sample. We demonstrate a case where retreatment with an alternative anti-VEGF agent resulted in worsening vision and vasculitis.
Purpose: To determine the efficacy, durability, and safety of combination intravitreal ranibizuma... more Purpose: To determine the efficacy, durability, and safety of combination intravitreal ranibizumab plus peripheral scatter laser in patients with macular edema secondary to branch retinal vein occlusion associated with peripheral retinal nonperfusion on ultrawide-field fluorescein angiography. Methods: A 12-month, randomized, controlled, prospective, single center phase I/II study of 12 treatment-naïve eyes of 12 patients with visual impairment secondary to macular edema secondary to branch retinal vein occlusion associated with peripheral nonperfusion on ultrawide-field fluorescein angiography. Patients were randomized in 1:1 fashion to study and control groups. Patients in the study group received angiography-guided peripheral scatter laser treatment at baseline. All patients received six monthly intravitreal injections of ranibizumab followed by six months of observation with pro re nata treatment with ranibizumab if prespecified visual acuity or optical coherence tomography criteria were met. Results: At the 6-month primary outcome, both groups had significant improvement in mean change in best-corrected visual acuity (treatment: +16.8 letters v/s control +14.5 letters) and reduction in central foveal thickness (treatment: -207 μ m v/s control -241 μ m). Both groups also had an improvement at 12 months in mean change in best-corrected visual acuity (treatment: +19.1 letters v/s control +15.3 letters) and reduction in central foveal thickness (treatment: -282 μ m v/s control -281 μ m). The differences between groups were not statistically significant. In the 6-month observation period, the REVOLUTIONARY group had a statistically-significant fewer number of retreatments (median of 1 in the treatment group v/s 2.5 in the control group p=0.03), and there was a trend in the reduction of patients needing retreatment (67% in the treatment group v/s 100% in the control group, p=0.14). Conclusion: This pilot study suggests safety and durability of combination ranibizumab + angiography-guided peripheral scatter laser in treatment-naïve patients with macular edema secondary to branch retinal vein occlusion and peripheral nonperfusion on ultrawide-field fluorescein angiography. Further investigation is warranted to demonstrate the efficacy and long-term benefit of this treatment strategy.
Purpose: To report the rates of postintravitreal injection (IVT) endophthalmitis with topical con... more Purpose: To report the rates of postintravitreal injection (IVT) endophthalmitis with topical conjunctival application of various concentrations of povidone-iodine (PI), including no PI. Methods: Retrospective chart review of patients receiving IVTs performed in a single practice between January 2011 and June 2016. Concentration of PI for all injections was recorded and cases of endophthalmitis identified and reviewed. Results: A total of 35,060 IVTs in 1854 patients were included from the 5.5-year period. 29,281 injections were performed with standard 5% PI, 5,460 injections with diluted PI (3,731 with 2.5%, 1,673 with 1.25%, 56 with 0.625%), and 319 IVTs with no PI. Incidence of patient-reported PI sensitivity occurred in 15.9% of patients. Fourteen cases of endophthalmitis were identified: 12 in eyes that received 5% PI, one in an eye that received 1.25% PI, and one in an eye receiving no PI. The incidence of endophthalmitis was 0.04% for 5% PI, 0.02% for dilute PI, and 0.31% for...
Mutations in the ORF15 exon of the RPGR gene cause a common form of X-linked retinitis pigmentosa... more Mutations in the ORF15 exon of the RPGR gene cause a common form of X-linked retinitis pigmentosa, which often results in severe loss of vision. In dogs and mice, gene augmentation therapy has been shown to arrest the progressive degeneration of rod and cone photoreceptors. However, the distribution of potentially treatable photoreceptors across the human retinas and the rate of degeneration are not known. Here, we have defined structural and functional features of the disease in 70 individuals with ORF15 mutations. We also correlated the features observed in patients with those of three Rpgr-mutant (Rpgr-ko, Rd9, and Rpgr-cko) mice. In patients, there was pronounced macular disease. Across the retina, rod and cone dysfunction showed a range of patterns and a spectrum of severity between individuals, but a high symmetry was observed between eyes of each individual. Genotype was not related to disease expression. In the Rpgr-ko mice, there were intraretinal differences in rhodopsin and cone opsin trafficking. In Rd9 and Rpgr-cko mice, retinal degeneration showed interocular symmetry. Longitudinal results in patients revealed localized rod and cone dysfunction with progression rates of 0.8 to 1.3 log per decade in sensitivity loss. Relatively retained rod and cone photoreceptors in mid-and far-peripheral temporal-inferior and nasal-inferior visual field regions should be good targets for future localized gene therapies in patients. †J.C. and A.V.C. contributed equally to this study.
Purpose: To describe a case of fulminant bilateral papillitis and chorioretinitis in the setting ... more Purpose: To describe a case of fulminant bilateral papillitis and chorioretinitis in the setting of positive coxsackievirus B titers, which convalesced months after the patient's presentation. The patient presented with an acute posterior multifocal placoid pigment epitheliopathy-like clinical picture and her visual acuity and visual field improved moderately after initiation of treatment with intravenous immunoglobulin. Methods: Case report of a white female with bilateral blurred vision is presented in this study. Results: A previously healthy 59-year-old white woman presented with a 3-day history of bilateral blurred vision. Initial visual acuity was hand motion in the right eye and count fingers in the left eye. Extensive workup and imaging was done and she was empirically started on intravenous antibiotics followed 24 hours later by intravenous steroids. The patient was found to have high titers of coxsackievirus B and sustained modest visual acuity and perimetry improvement in one eye after intravenous immunoglobulin infusion. Conclusion: A case of fulminant bilateral chorioretinitis and papillitis that resulted in bilateral vision loss despite high-dose steroids within 24 hours of initial loss in vision is presented in this study. The patient was found to have high titers of coxsackievirus B3, B4, B5 after presentation and her condition improved after treatment with intravenous immunoglobulin, suggesting a plausible immune component.
Proof of concept for MERTK gene replacement therapy has been demonstrated using different viral v... more Proof of concept for MERTK gene replacement therapy has been demonstrated using different viral vectors in the Royal College of Surgeon (RCS) rat, a well characterized model of recessive retinitis pigmentosa that contains a mutation in the Mertk gene. MERTK plays a key role in renewal of photoreceptor outer segments (OS) by phagocytosis of shed OS tips. Mutations in MERTK cause impaired phagocytic activity and accumulation of OS debris in the interphotoreceptor space that ultimately leads to photoreceptor cell death. In the present study, we conducted a series of preclinical potency and GLP-compliant safety evaluations of an adeno-associated virus type 2 (AAV2) vector expressing human MERTK cDNA driven by the retinal pigment epithelium-specific, VMD2 promoter. We demonstrate the potency of the vector in RCS rats by improved electroretinogram (ERG) responses in treated eyes compared with contralateral untreated controls. Toxicology and biodistribution studies were performed in Sprague-Dawley (SD) rats injected with two different doses of AAV vectors and buffer control. Delivery of vector in SD rats did not result in a change in ERG amplitudes of rod and cone responses relative to balanced salt solution control-injected eyes, indicating that administration of AAV vector did not adversely affect normal retinal function. In vivo fundoscopic analysis and postmortem retinal morphology of the vector-injected eyes were normal compared with controls. Evaluation of blood smears showed the lack of transformed cells in the treated eyes. All injected eyes and day 1 blood samples were positive for vector genomes, and all peripheral tissues were negative. Our results demonstrate the potency and safety of the AAV2-VMD2-hMERTK vector in animal models tested. A GMP vector has been manufactured and is presently in clinical trial.
A 52-year-old, immune-suppressed man presented with painful proptosis. Orbital imaging revealed e... more A 52-year-old, immune-suppressed man presented with painful proptosis. Orbital imaging revealed enhancement of his right inferior rectus muscle and mild ethmoidal sinus disease. Sinus washings and turbinectomy demonstrated Curvularia. Despite aggressive intravenous antimicrobials, the patient remained febrile. Repeat imaging demonstrated a well-defined intramuscular abscess without contiguous orbital or paranasal involvement. Following surgical drainage, the patient improved. Cultures of the material expressed from the abscess confirmed a co-infection with Fusarium. Although rare, fungal abscess of the extraocular muscle should be considered in patients (particularly if immunosuppressed) with extraocular muscle enlargement resistant to conventional antimicrobial therapy. Prompt diagnosis and treatment could potentially prevent further serious morbidity or mortality. (
Cobalt is a widely used in the industrial production of hard metals. Cobalt ingestion has been re... more Cobalt is a widely used in the industrial production of hard metals. Cobalt ingestion has been reported to cause widespread systemic toxicity, but its effects on vision have been sparsely reported. The authors report the case of a patient who ingested cattle magnets, which remained in his stomach for an unknown duration of time. These magnets largely consist of cobalt that gradually leached into his blood stream, resulting in protean systemic manifestations, which included optic atrophy.
Cobalt is a widely used in the industrial production of hard metals. Cobalt ingestion has been re... more Cobalt is a widely used in the industrial production of hard metals. Cobalt ingestion has been reported to cause widespread systemic toxicity, but its effects on vision have been sparsely reported. The authors report the case of a patient who ingested cattle magnets, which remained in his stomach for an unknown duration of time. These magnets largely consist of cobalt that gradually leached into his blood stream, resulting in protean systemic manifestations, which included optic atrophy.
Objective-To determine safety and efficacy of subretinal gene therapy in the RPE65 form of Leber ... more Objective-To determine safety and efficacy of subretinal gene therapy in the RPE65 form of Leber congenital amaurosis using recombinant adeno-associated virus 2 (rAAV2) carrying human RPE65 gene.
Purpose: To evaluate the safety and efficacy of a dexamethasone sustained-release intracanalicula... more Purpose: To evaluate the safety and efficacy of a dexamethasone sustained-release intracanalicular insert (DII) (Dextenza ® Ocular Therapeutix, Inc., Bedford, MA) for control of inflammation and pain after pars plana vitrectomy (PPV) compared to standard topical steroid therapy. Methods: Retrospective, case-matched comparison of consecutive patients undergoing PPV. Control patients were matched by diagnosis and procedure performed. The primary outcome was the proportion of patients with complete anterior chamber cell clearance (ACCC) at postoperative day 7. Secondary outcomes included proportion developing intraocular pressure (IOP) >25 mmHg, change in mean optical coherence tomography central foveal thickness (OCT CFT), and proportion developing cystoid macular edema (CME) on qualitative analysis of OCT. The DII group had a statistically significant higher rate of complete ACCC compared to the topical steroid group (65% versus 35%, respectively, with p=0.01). No eyes had IOP >25 mmHg in the DII, compared to 2 eyes in the topical steroid group (not statistically significant). Overall, mean OCT CFT decreased in both groups; one patient had CME in the DII group, as compared to three in the topical steroid group (not statistically significant). The dexamethasone intracanalicular insert provided excellent safety and efficacy in control of postoperative inflammation following PPV in this retrospective casematched study.
Mutations in the ORF15 exon of the RPGR gene cause a common form of X-linked retinitis pigmentosa... more Mutations in the ORF15 exon of the RPGR gene cause a common form of X-linked retinitis pigmentosa, which often results in severe loss of vision. In dogs and mice, gene augmentation therapy has been shown to arrest the progressive degeneration of rod and cone photoreceptors. However, the distribution of potentially treatable photoreceptors across the human retinas and the rate of degeneration are not known. Here, we have defined structural and functional features of the disease in 70 individuals with ORF15 mutations. We also correlated the features observed in patients with those of three Rpgr-mutant (Rpgr-ko, Rd9, and Rpgr-cko) mice. In patients, there was pronounced macular disease. Across the retina, rod and cone dysfunction showed a range of patterns and a spectrum of severity between individuals, but a high symmetry was observed between eyes of each individual. Genotype was not related to disease expression. In the Rpgr-ko mice, there were intraretinal differences in rhodopsin and cone opsin trafficking. In Rd9 and Rpgr-cko mice, retinal degeneration showed interocular symmetry. Longitudinal results in patients revealed localized rod and cone dysfunction with progression rates of 0.8 to 1.3 log per decade in sensitivity loss. Relatively retained rod and cone photoreceptors in mid-and far-peripheral temporal-inferior and nasal-inferior visual field regions should be good targets for future localized gene therapies in patients. †J.C. and A.V.C. contributed equally to this study.
The laboratory rat (Rattus norvegicus) is a key animal model for biomedical research. However, th... more The laboratory rat (Rattus norvegicus) is a key animal model for biomedical research. However, the genetic infrastructure required for connecting phenotype and genotype in the rat is currently incomplete. Here, we report the construction and integration of two genomic maps: a dense genetic linkage map of the rat and the first radiation hybrid (RH) map of the rat. The genetic map was constructed in two F2 intercrosses (SHRSP × BN and FHH × ACI), containing a total of 4736 simple sequence length polymorphism (SSLP) markers. Allele sizes for 4328 of the genetic markers were characterized in 48 of the most commonly used inbred strains. The RH map is a lod ≥ 3 framework map, including 983 SSLPs, thereby allowing integration with markers on various genetic maps and with markers mapped on the RH panel. Together, the maps provide an integrated reference to >3000 genes and ESTs and >8500 genetic markers (5211 of our SSLPs and >3500 SSLPs developed by other groups). [Bihoreau et al. ...
Purpose: To evaluate the safety and efficacy of a dexamethasone sustained-release intracanalicula... more Purpose: To evaluate the safety and efficacy of a dexamethasone sustained-release intracanalicular insert (DII) (Dextenza ® Ocular Therapeutix, Inc., Bedford, MA) for control of inflammation and pain after pars plana vitrectomy (PPV) compared to standard topical steroid therapy. Methods: Retrospective, case-matched comparison of consecutive patients undergoing PPV. Control patients were matched by diagnosis and procedure performed. The primary outcome was the proportion of patients with complete anterior chamber cell clearance (ACCC) at postoperative day 7. Secondary outcomes included proportion developing intraocular pressure (IOP) >25 mmHg, change in mean optical coherence tomography central foveal thickness (OCT CFT), and proportion developing cystoid macular edema (CME) on qualitative analysis of OCT. The DII group had a statistically significant higher rate of complete ACCC compared to the topical steroid group (65% versus 35%, respectively, with p=0.01). No eyes had IOP >25 mmHg in the DII, compared to 2 eyes in the topical steroid group (not statistically significant). Overall, mean OCT CFT decreased in both groups; one patient had CME in the DII group, as compared to three in the topical steroid group (not statistically significant). The dexamethasone intracanalicular insert provided excellent safety and efficacy in control of postoperative inflammation following PPV in this retrospective casematched study.
American Journal of Ophthalmology Case Reports, 2020
To describe the clinical and pathologic characteristics of a case of retinal vasculitis and vitri... more To describe the clinical and pathologic characteristics of a case of retinal vasculitis and vitritis following brolucizumab administration and subsequent ranibizumab treatment. Observations: A 76-year old Caucasian woman experienced pain, decreased vision and floaters one week after receiving her third monthly intravitreal brolucizumab injection in the right eye for exudative age-related macular degeneration. Examination was significant for 0.5+ anterior chamber cells, vitritis, mild peripheral vascular sheathing, and decreased vision from 20/70 to 20/200. She was started on topical 1% prednisolone acetate with improvement in her examination. She was switched to ranibizumab one month after her last brolucizumab injection of the right eye. Three weeks after her ranibizumab injection, she noticed photophobia, pain and decreased vision. Examination revealed worsening uveitis, vitritis, vascular sheathing, and decreased vision to count fingers. Despite starting on 0.05% difluprednate drops every 2 hours and oral high-dose methylprednisolone, the patient did not have any significant improvement in her symptoms or examination. She underwent pars plana vitrectomy and vitreous biopsy with intravitreal triamcinolone injection to the right eye. Vitreous biopsy and culture ruled out infectious endophthalmitis, and further cytopathologic analysis revealed chronic inflammatory infiltrate. Treatment with brolucizumab can result in intraocular inflammation and retinal vasculitis likely due to a delayed hypersensitivity reaction to the drug, supported by cytopathologic analysis of a vitreous sample. We demonstrate a case where retreatment with an alternative anti-VEGF agent resulted in worsening vision and vasculitis.
Purpose: To determine the efficacy, durability, and safety of combination intravitreal ranibizuma... more Purpose: To determine the efficacy, durability, and safety of combination intravitreal ranibizumab plus peripheral scatter laser in patients with macular edema secondary to branch retinal vein occlusion associated with peripheral retinal nonperfusion on ultrawide-field fluorescein angiography. Methods: A 12-month, randomized, controlled, prospective, single center phase I/II study of 12 treatment-naïve eyes of 12 patients with visual impairment secondary to macular edema secondary to branch retinal vein occlusion associated with peripheral nonperfusion on ultrawide-field fluorescein angiography. Patients were randomized in 1:1 fashion to study and control groups. Patients in the study group received angiography-guided peripheral scatter laser treatment at baseline. All patients received six monthly intravitreal injections of ranibizumab followed by six months of observation with pro re nata treatment with ranibizumab if prespecified visual acuity or optical coherence tomography criteria were met. Results: At the 6-month primary outcome, both groups had significant improvement in mean change in best-corrected visual acuity (treatment: +16.8 letters v/s control +14.5 letters) and reduction in central foveal thickness (treatment: -207 μ m v/s control -241 μ m). Both groups also had an improvement at 12 months in mean change in best-corrected visual acuity (treatment: +19.1 letters v/s control +15.3 letters) and reduction in central foveal thickness (treatment: -282 μ m v/s control -281 μ m). The differences between groups were not statistically significant. In the 6-month observation period, the REVOLUTIONARY group had a statistically-significant fewer number of retreatments (median of 1 in the treatment group v/s 2.5 in the control group p=0.03), and there was a trend in the reduction of patients needing retreatment (67% in the treatment group v/s 100% in the control group, p=0.14). Conclusion: This pilot study suggests safety and durability of combination ranibizumab + angiography-guided peripheral scatter laser in treatment-naïve patients with macular edema secondary to branch retinal vein occlusion and peripheral nonperfusion on ultrawide-field fluorescein angiography. Further investigation is warranted to demonstrate the efficacy and long-term benefit of this treatment strategy.
Purpose: To report the rates of postintravitreal injection (IVT) endophthalmitis with topical con... more Purpose: To report the rates of postintravitreal injection (IVT) endophthalmitis with topical conjunctival application of various concentrations of povidone-iodine (PI), including no PI. Methods: Retrospective chart review of patients receiving IVTs performed in a single practice between January 2011 and June 2016. Concentration of PI for all injections was recorded and cases of endophthalmitis identified and reviewed. Results: A total of 35,060 IVTs in 1854 patients were included from the 5.5-year period. 29,281 injections were performed with standard 5% PI, 5,460 injections with diluted PI (3,731 with 2.5%, 1,673 with 1.25%, 56 with 0.625%), and 319 IVTs with no PI. Incidence of patient-reported PI sensitivity occurred in 15.9% of patients. Fourteen cases of endophthalmitis were identified: 12 in eyes that received 5% PI, one in an eye that received 1.25% PI, and one in an eye receiving no PI. The incidence of endophthalmitis was 0.04% for 5% PI, 0.02% for dilute PI, and 0.31% for...
Mutations in the ORF15 exon of the RPGR gene cause a common form of X-linked retinitis pigmentosa... more Mutations in the ORF15 exon of the RPGR gene cause a common form of X-linked retinitis pigmentosa, which often results in severe loss of vision. In dogs and mice, gene augmentation therapy has been shown to arrest the progressive degeneration of rod and cone photoreceptors. However, the distribution of potentially treatable photoreceptors across the human retinas and the rate of degeneration are not known. Here, we have defined structural and functional features of the disease in 70 individuals with ORF15 mutations. We also correlated the features observed in patients with those of three Rpgr-mutant (Rpgr-ko, Rd9, and Rpgr-cko) mice. In patients, there was pronounced macular disease. Across the retina, rod and cone dysfunction showed a range of patterns and a spectrum of severity between individuals, but a high symmetry was observed between eyes of each individual. Genotype was not related to disease expression. In the Rpgr-ko mice, there were intraretinal differences in rhodopsin and cone opsin trafficking. In Rd9 and Rpgr-cko mice, retinal degeneration showed interocular symmetry. Longitudinal results in patients revealed localized rod and cone dysfunction with progression rates of 0.8 to 1.3 log per decade in sensitivity loss. Relatively retained rod and cone photoreceptors in mid-and far-peripheral temporal-inferior and nasal-inferior visual field regions should be good targets for future localized gene therapies in patients. †J.C. and A.V.C. contributed equally to this study.
Purpose: To describe a case of fulminant bilateral papillitis and chorioretinitis in the setting ... more Purpose: To describe a case of fulminant bilateral papillitis and chorioretinitis in the setting of positive coxsackievirus B titers, which convalesced months after the patient's presentation. The patient presented with an acute posterior multifocal placoid pigment epitheliopathy-like clinical picture and her visual acuity and visual field improved moderately after initiation of treatment with intravenous immunoglobulin. Methods: Case report of a white female with bilateral blurred vision is presented in this study. Results: A previously healthy 59-year-old white woman presented with a 3-day history of bilateral blurred vision. Initial visual acuity was hand motion in the right eye and count fingers in the left eye. Extensive workup and imaging was done and she was empirically started on intravenous antibiotics followed 24 hours later by intravenous steroids. The patient was found to have high titers of coxsackievirus B and sustained modest visual acuity and perimetry improvement in one eye after intravenous immunoglobulin infusion. Conclusion: A case of fulminant bilateral chorioretinitis and papillitis that resulted in bilateral vision loss despite high-dose steroids within 24 hours of initial loss in vision is presented in this study. The patient was found to have high titers of coxsackievirus B3, B4, B5 after presentation and her condition improved after treatment with intravenous immunoglobulin, suggesting a plausible immune component.
Proof of concept for MERTK gene replacement therapy has been demonstrated using different viral v... more Proof of concept for MERTK gene replacement therapy has been demonstrated using different viral vectors in the Royal College of Surgeon (RCS) rat, a well characterized model of recessive retinitis pigmentosa that contains a mutation in the Mertk gene. MERTK plays a key role in renewal of photoreceptor outer segments (OS) by phagocytosis of shed OS tips. Mutations in MERTK cause impaired phagocytic activity and accumulation of OS debris in the interphotoreceptor space that ultimately leads to photoreceptor cell death. In the present study, we conducted a series of preclinical potency and GLP-compliant safety evaluations of an adeno-associated virus type 2 (AAV2) vector expressing human MERTK cDNA driven by the retinal pigment epithelium-specific, VMD2 promoter. We demonstrate the potency of the vector in RCS rats by improved electroretinogram (ERG) responses in treated eyes compared with contralateral untreated controls. Toxicology and biodistribution studies were performed in Sprague-Dawley (SD) rats injected with two different doses of AAV vectors and buffer control. Delivery of vector in SD rats did not result in a change in ERG amplitudes of rod and cone responses relative to balanced salt solution control-injected eyes, indicating that administration of AAV vector did not adversely affect normal retinal function. In vivo fundoscopic analysis and postmortem retinal morphology of the vector-injected eyes were normal compared with controls. Evaluation of blood smears showed the lack of transformed cells in the treated eyes. All injected eyes and day 1 blood samples were positive for vector genomes, and all peripheral tissues were negative. Our results demonstrate the potency and safety of the AAV2-VMD2-hMERTK vector in animal models tested. A GMP vector has been manufactured and is presently in clinical trial.
A 52-year-old, immune-suppressed man presented with painful proptosis. Orbital imaging revealed e... more A 52-year-old, immune-suppressed man presented with painful proptosis. Orbital imaging revealed enhancement of his right inferior rectus muscle and mild ethmoidal sinus disease. Sinus washings and turbinectomy demonstrated Curvularia. Despite aggressive intravenous antimicrobials, the patient remained febrile. Repeat imaging demonstrated a well-defined intramuscular abscess without contiguous orbital or paranasal involvement. Following surgical drainage, the patient improved. Cultures of the material expressed from the abscess confirmed a co-infection with Fusarium. Although rare, fungal abscess of the extraocular muscle should be considered in patients (particularly if immunosuppressed) with extraocular muscle enlargement resistant to conventional antimicrobial therapy. Prompt diagnosis and treatment could potentially prevent further serious morbidity or mortality. (
Cobalt is a widely used in the industrial production of hard metals. Cobalt ingestion has been re... more Cobalt is a widely used in the industrial production of hard metals. Cobalt ingestion has been reported to cause widespread systemic toxicity, but its effects on vision have been sparsely reported. The authors report the case of a patient who ingested cattle magnets, which remained in his stomach for an unknown duration of time. These magnets largely consist of cobalt that gradually leached into his blood stream, resulting in protean systemic manifestations, which included optic atrophy.
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Papers by Marc Peden