Jiong Yan

Transduction of photoreceptors with equine infectious anemia virus lentiviral vectors: safety and biodistribution of StarGen for Stargardt disease.

PURPOSE StarGen is an equine infectious anemia virus (EIAV)-based lentiviral vector that expresses the photoreceptor-specific adenosine triphosphate (ATP)-binding cassette transporter (ABCA4) protein that is mutated in Stargardt disease (STGD1), a juvenile macular dystrophy. EIAV vectors are able to efficiently transduce rod and cone photoreceptors in addition to retinal pigment epithelium in the adult macaque and rabbit retina following subretinal delivery. The safety and biodistribution of StarGen following subretinal delivery in macaques and rabbits was assessed. METHODS Regular ophthalmic examinations, IOP measurements, ERG responses, and histopathology were carried out in both species to compare control and vector-treated eyes. Tissue and fluid samples were obtained to evaluate the persistence, biodistribution, and shedding of the vector following subretinal delivery. RESULTS Ophthalmic examinations revealed a slightly higher level of inflammation in StarGen compared with control treated eyes in both species. However, inflammation was transient and no overt toxicity was observed in StarGen treated eyes and there were no abnormal clinical findings. There was no StarGen-associated rise in IOP or abnormal ERG response in either rabbits or macaques. Histopathologic examination of the eyes did not reveal any detrimental changes resulting from subretinal administration of StarGen. Although antibodies to StarGen vector components were detected in rabbit but not macaque serum, this immunologic response did not result in any long-term toxicity. Biodistribution analysis demonstrated that the StarGen vector was restricted to the ocular compartment. CONCLUSIONS In summary, these studies demonstrate StarGen to be well tolerated and localized following subretinal administration.

Visual outcomes and incidence of recurrent vitreous hemorrhage after vitrectomy in diabetic eyes pretreated with bevacizumab (avastin).

Purpose: To evaluate the safety and effect of bevacizumab pretreatment on the incidence of recurrent vitreous hemorrhage and visual acuity after vitrectomy for proliferative diabetic retinopathy. Methods: This was a consecutive, retrospective, and comparative cohort study. Patients undergoing vitrectomy from September 2006 through November 2007 at the Emory Eye Center for complications of proliferative diabetic retinopathy were identified and reviewed. A total of 33 eyes pretreated with bevacizumab and 104 untreated eyes were observed for postoperative vitreous hemorrhage and final visual acuity. Results: Patients in the bevacizumab group were significantly younger than those in the untreated group (average age, 46.4 vs. 58.4 years) and were more likely to have 20-gauge instrumentation (58% vs. 36%). An average of 9.6 days passed between injection and surgery. Early (4-6 weeks) rebleed rates were 15% versus 13% in the bevacizumab and untreated groups, respectively, and not statistically different. Preoperative (7/200 vs. count finger at 4′), 1-month postoperative (20/200−3 vs. 20/150), and 3-month postoperative visual acuity (20/100−3 vs. 20/100+2) were not statistically different between groups. No statistical difference was found in rebleed rates regarding the gauge of vitrectomy. Conclusion: Bevacizumab pretreatment for diabetic vitrectomy was not associated with any observed complications but did not influence rates of postoperative vitreous hemorrhage or final visual acuity in this retrospective series. The overall incidence of postoperative early vitreous hemorrhage in this series was 13% and seems lower than historically reported rates.

Topical Ketorolac in Vitreoretinal Surgery: A Prospective, Randomized, Placebo-Controlled, Double-Masked Trial

OBJECTIVE To evaluate the effects of topical ketorolac in patients undergoing vitreoretinal surgery. METHODS One hundred nine patients undergoing vitrectomies were randomized to receive either topical ketorolac tromethamine, 0.4%, or placebo. Patients were instructed to begin taking the study medication 3 days preoperatively (4 times daily) and to continue taking it 4 weeks postoperatively. MAIN OUTCOME MEASURES Intraoperative pupil diameter, postoperative day 1 pain and inflammation, 1-month postoperative retinal thickness, and preoperative and 1-month postoperative best-corrected visual acuities. RESULTS The difference in mean pupil diameters between patients using ketorolac and those taking placebo was 0.06 mm (P = .39). Patients taking ketorolac and those taking placebo had mean pain scores (scale, 1-10) of 0.24 (SD, 0.6) and 1.06 (SD, 2) (P = .03) and mean inflammation grades (grade, 0-4) of 0.59 (SD, 0.7) and 1.16 (SD, 0.9) (P < .001), respectively. Ketorolac reduced central subfield thickness by 8%, but this was not statistically significant. At 1 month, mean visual acuities improved to 0.40 logMAR units (mean Snellen, 20/50; SD, 0.28 logMAR units) in the ketorolac group from 0.83 logMAR units (20/150(+2); SD, 0.60 logMAR units) at baseline and to 0.67 logMAR units (20/100(+1); SD, 0.46 logMAR units) in the placebo group from 0.92 logMAR units (20/150(-2); SD, 0.62 logMAR units) at baseline (P = .001). CONCLUSIONS Topical ketorolac was well tolerated and safe, reduced postoperative pain and inflammation, and improved visual recovery in this prospective, double-masked trial. APPLICATION TO CLINICAL PRACTICE Topical ketorolac may benefit patients undergoing vitreoretinal surgery. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00576329.

Incidence of Postvitrectomy Macular Edema Using Optical Coherence Tomography

OBJECTIVE To evaluate the incidence, effect on visual recovery, and predisposing risk factors of postvitrectomy macular edema (ME). DESIGN Prospective cohort study. PARTICIPANTS One-hundred nine eyes undergoing nonemergent vitrectomy surgery. METHODS Eyes were evaluated for postoperative day 1 inflammation, 1-month retinal thickness using optical coherence tomography, and preoperative and 1-month postoperative best-corrected visual acuity (BCVA). Macular edema was defined as central subfield thickness > or =272 microm. MAIN OUTCOME MEASURES Retinal thickness, inflammation, and BCVA. RESULTS Incidence of ME on optical coherence tomography was 47% (95% confidence interval [CI], 37%-56%). Mean 1-month visual acuity improved 3.3 lines (0.33 logarithm of minimum angle of resolution [logMAR] units) to 20/80(+1) (0.58+/-0.46 logMAR units) from 20/150(-2) (0.91+/-0.63 logMAR units) before surgery (P<0.001). Mean 1-month center point thickness (CPT), central subfield (CSF), and total macular volume were 265+/-107 microm, 288+/-94 microm, and 7.8+/-1.2 mm(3), respectively. Severity of postoperative inflammation predicted retinal thickness at 1 month (P<0.05). Intraoperative epinephrine use was associated with increased postoperative inflammation (P = 0.02). Eyes with greater reduction in CSF (or CPT) from baseline experienced more rapid visual recovery (r = -0.36; 95% CI, -0.61 to -0.06; P = 0.02). CONCLUSIONS Postvitrectomy ME is common and delays visual recovery. Degree of postoperative inflammation is an important risk factor for ME and, in this series, was increased in the setting of intraocular epinephrine. Efforts to reduce or prevent inflammation after vitrectomy should be beneficial and therefore are encouraged.

Clinical characteristics of hydroxychloroquine retinopathy

Aims To assess the characteristics and outcomes of patients with hydroxychloroquine retinopathy and to review the current screening guidelines. Methods Retrospective chart review of patients diagnosed as having hydroxychloroquine retinopathy at our institution between 2004 and 2008. Results All seven patients were women. While every patient received 400 mg of hydroxychloroquine per day, every patient exceeded the recommended daily dosage allowance (6.5 mg/kg/day). The mean daily dose of hydroxychloroquine was 8.2 mg/kg/day (range: 6.8–13.6 mg/kg/day). The mean duration of usage was 16.3 years (range: 8.5–30 years), and the mean cumulative dose was 2377 g (range: 1241–4380 g). The mean visual acuity at presentation was 20/30, but all patients exhibited significant visual-field defects. Colour vision was impaired in six patients. Four patients exhibited granular hyperpigmentation in the central macula, and three had a bulls eye appearance. The mean follow-up time was 21 months. The visual outcomes remained stable for every patient except for one patient who experienced an improvement in visual function after drug cessation. Conclusions Hydroxychloroquine retinopathy, although rare, still exists despite current screening guidelines. The authors recommend that physicians dose hydroxychloroquine according to lean body weight and that they use risk stratification to guide their screening regimens.

Fundus autofluorescence features in the inflammatory maculopathies

Purpose To describe the fundus autofluorescence (FAF) features of the inflammatory maculopathies and develop a quantification method for FAF analysis. Methods This is a retrospective, consecutive case series of patients with inflammatory maculopathies from two tertiary centers. The clinical findings, demographics, and FAF imaging characteristics were reviewed. Foveal autofluorescence (AF) was analyzed. Median and standard deviation (SD) of foveal AF intensity were measured. Results Thirty eyes of 15 patients were evaluated with both qualitative and quantitative FAF analysis. In acute macular neuroretinopathy, the active phase showed foveal hypoautofluorescence, which became hypoautofluorescent with resolution. In acute posterior multifocal placoid pigment epitheliopathy, multiple lesions with hypoautofluorescent centers with hyperautofluorescent borders were observed in active disease and became hypoautofluorescent with disease convalescence. In multifocal choroiditis and punctate inner choroiditis, the active hyperautofluorescent lesions progressed to inactive, hypoautofluorescent scars. Active serpiginous choroiditis showed hyperautofluorescent borders adjacent to a helicoid-shaped, hypoautofluorescent scar. Active unilateral acute idiopathic maculopathy (UAIM) showed a complex pattern of hypo- and hyperautoflourescence in the macula. The median foveal AF was the greatest in acute macular neuroretinopathy and UAIM among the maculopathies, while the greatest SD of foveal AF intensity was observed in UAIM. Conclusion The active phase of the majority of inflammatory maculopathies was characterized by hyperautofluorescent lesions. Increased SD of foveal AF correlated with a mixture of hypo-and hyperautoflourescence. Median and SD may be useful metrics in foveal AF and quantifiable values that may be assessed over time as a disease process evolves. Improvements in quantification methods of FAF imaging may allow us to objectively evaluate posterior uveitis.

Residual triamcinolone acetonide sequestered in the fovea after macular hole repair.

Purpose: To report the macular hole closure rate and visual outcomes of patients with residual triamcinolone acetonide in the fovea after macular hole repair. Methods: We reviewed the medical records of consecutive patients who underwent macular hole surgery at our institution between 2005 and 2008. Only patients with visible triamcinolone in the fovea in the first postoperative month were included. Results: Six patients with Stage III or IV macular holes were included. All patients underwent pars plana vitrectomy, internal limiting membrane peeling, and gas tamponade. Triamcinolone acetonide was used to visualize the vitreous in every patient, and diluted indocyanine green was used to stain the internal limiting membrane in five patients. The median preoperative best-corrected visual acuity was 20/200, which improved to a median of 20/40 at the last follow-up. Five patients eventually developed retinal pigment epithelial alterations. Anatomic hole closure was achieved in every patient. The mean follow-up was 23 months (range, 3-36 months). Conclusion: Residual triamcinolone sequestered in the fovea after macular hole surgery did not affect hole closure or prevent improvement in visual acuity. It is unclear whether the retinal pigment epithelial alterations in our patients represent toxicity or are unrelated to the triamcinolone exposure.

Physical Activity and Quality of Life in Retinitis Pigmentosa.

Purpose Aerobic exercise has been found to be neuroprotective in animal models of retinal degeneration. This study aims to report physical activity levels in patients with RP and investigate the relationship between physical activity and vision-related quality-of-life (QOL). Materials and Methods A retrospective study of adult patients with RP examined in 2005–2014. Physical activity levels were assessed using the Godin Exercise Questionnaire. The NEI-Visual Function Questionaire-25 (VFQ-25), SF-36 General Health survey, and Pepper Assessment Tool for Disability (PAT-D) were administered. Results 143 patients participated. 81 (56.6%) patients were classified as “active” and 62 (43.4%) as “insufficiently active” by Godin score. VFQ-25 revealed statistically significant differences between the active and insufficiently active patients, including overall visual function (53.3 versus 45.1, p = 0.010), color vision (73.8 versus 52.9, p < 0.001), and peripheral vision (34.3 versus 23.8, p = 0.021). The physical component of the SF-36 and the PAT-D survey also demonstrated statistically significant differences (47.2 versus 52.9, p = 0.002; 24.3 versus 30.0, p = 0.010). Active patients had a higher initial Goldmann visual field (GVF) score (74.8 versus 60.1 degrees, p = 0.255) and final GVF score (78.7 versus 47.1 degrees, p = 0.069) but did not reach statistical significance. Conclusions In RP, increased physical activity is associated with greater self-reported visual function and QOL.

Pericentral hydroxychloroquine retinopathy in a Caucasian female

Purpose To report a rare presentation of the pericentral pattern of hydroxychloroquine (HCQ) retinal toxicity in a Caucasian female. Observations The patient presented with 20 years of exposure to HCQ, at a daily dose of 5.2mg/kg of actual body weight, and manifested a pericentral-only phenotype of HCQ toxicity, as demonstrated with detailed structural and functional testing. Conclusions and importance Although rare, the pericentral pattern of HCQ toxicity may occur in Caucasian patients in the absence of paracentral changes.

Atypical presentation of neuronal ceroid lipofuscinosis type 8 in a sibling pair and review of the eye findings and neurological features

Purpose To report atypical presentation of neuronal ceroid lipofuscinoses type 8 (CLN8) to the eye clinic and review clinical features of CLN8. Observations Detailed eye exam by slit lamp exam, indirect ophthalmoscopy, fundus photography, optical coherence tomography, visual fields and electroretinogram (ERG). Molecular genetic testing using Next Generation Sequencing panel (NGS) and array Comparative Genomic Hybridization (aCGH). The siblings in this study presented to the eye clinic with retinitis pigmentosa and cystoid macular edema, and a history of seizures but no severe neurocognitive deficits or regression. Genetic testing identified a c.200C > T (p.A67V) variant in the CLN8 gene and a deletion encompassing the entire gene. Electron microscopy of lymphocytes revealed fingerprint inclusions in both siblings. Conclusions and Importance: Pathogenic variants in CLN8 account for the retinitis pigmentosa and seizures in our patients however, currently, they do not have regression or neurocognitive decline. The presentation of NCL can be very diverse and it is important for ophthalmologists to consider this in the differential diagnosis of retinal disorders with seizures or other neurological features. Molecular genetic testing of multiple genes causing isolated and syndromic eye disorders using NGS panels and aCGH along with additional complementary testing may often be required to arrive at a definitive diagnosis.