Purtscher-like retinopathy in a 19-year-old with maturity-onset diabetes of the young: a case report.

BACKGROUND: We report the first case of Purtscher-like retinopathy in a patient with 17q12 deletion-associated maturity-onset diabetes of the young. CASE PRESENTATION: A 19-year-old diabetic Hispanic male with history of cataracts and toe amputations presented with sudden onset of painless bilateral vision loss for 1 week with no associated trauma. Visual acuity was counting fingers at six feet in both eyes. Dilated retinal examination revealed bilateral peripapillary cotton wool spots and intraretinal hemorrhages, and significant subretinal and intraretinal fluid on optical coherence tomography. Fluorescein angiography revealed arteriolar staining and leakage around the disc with areas of capillary nonperfusion, supporting the diagnosis of Purtscher-like retinopathy. Systemic workup revealed multiple diabetic complications including chronic osteomyelitis of multiple toes, nonhealing diabetic foot ulcers, neurogenic bladder and bowel, and bilateral lower-extremity muscular neuropathies. Genetic evaluation revealed a 17q12 deletion, which is associated with maturity-onset diabetes of the young 5. On follow-up examination, he received a single intravitreal antivascular endothelial growth factor injection in the left eye (off label) for persistent macular edema. Although his retinal edema improved, his visual acuity remained poor. CONCLUSIONS: The presentation of our patient's multiple diabetic complications along visual symptoms suggests Purtscher-like retinopathy can be a sequela of uncontrolled diabetes. Purtscher-like retinopathy is a rare but possible consideration in diabetic patients who present with acute-onset vision loss.

Benign Lobular Inner Nuclear Layer Proliferations of the Retina Associated with Congenital Hypertrophy of the Retinal Pigment Epithelium.

PURPOSE: To report the clinical and imaging findings of 4 patients with benign intraretinal tumors, 2 of which were associated with retinal pigment epithelium (RPE) hypertrophy. To our knowledge, this condition has not been described previously and should be distinguished from retinoblastoma and other malignant retinal neoplasms. DESIGN: Retrospective case series. PARTICIPANTS: Four patients from 3 institutions. METHODS: Four patients with intraretinal tumors of the inner nuclear layer (INL) underwent a combination of ophthalmic examination, fundus photography, fluorescein angiography, OCT, OCT angiography, and whole exome sequencing. MAIN OUTCOME MEASURES: Description of multimodal imaging findings and systemic findings from 4 patients with benign intraretinal tumors and whole exome studies from 3 patients. RESULTS: Six eyes of 4 patients 5, 13, 32, and 27 years of age were found to have white intraretinal tumors that remained stable over the follow-up period (range, 9 months-4 years). The tumors were unilateral in 2 patients and bilateral in 2 patients. The tumors were white, centered on the posterior pole, and multifocal, with some consisting of multiple lobules with arching extensions that extended beyond the central tumor mass. OCT demonstrated these lesions to be centered within the INL at the border of the inner plexiform layer. In addition, 2 patients demonstrated congenital hypertrophy of the RPE (CHRPE) lesions. Three of 4 patients underwent whole exome sequencing of the blood that revealed no candidate variants that plausibly could account for the phenotype. CONCLUSIONS: We characterize a novel benign tumor of the INL that, in 2 patients, was associated with separate CHRPE lesions. We propose the term benign lobular inner nuclear layer proliferation to describe these lesions. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Changes in Treatment-Naive Pigment Epithelial Detachments Associated With the Initial Anti-Vascular Endothelial Growth Factor Injection: A Post Hoc Analysis From the HARBOR Trial.

Importance: Pigment epithelial detachment (PED) is a feature commonly associated with neovascular age-related macular degeneration (nAMD) and may be perceived as being difficult to treat. Therefore, this investigation explored changes in PEDs and visual acuity outcomes following an initial anti-vascular endothelial growth factor (VEGF) injection and identified factors associated with positive response. Objective: To describe changes in treatment-naive pigment epithelial detachments associated with the initial anti-VEGF injection. Design, Setting, and Participants: Post hoc analysis of patients from the Phase III, Double-masked, Multicenter, Randomized, Active Treatment-controlled Study of the Efficacy and Safety of 0.5 mg and 2.0 mg Ranibizumab Administered Monthly or on an As-needed Basis in Patients With Subfoveal Neovascular Age-Related Macular Degeneration (HARBOR) trial (NCT00891735) with PED at baseline. The HARBOR trial was a phase 3, randomized, multicenter, double-masked, active treatment-controlled trial. Participants included treatment-naive patients with subfoveal nAMD and PEDs at baseline; intervention arms were pooled for analysis (n = 586). The HARBOR study began in July 2009 and was completed in August 2012, and the post hoc analyses were conducted between October 2016 and May 2018. Interventions: Intravitreal injections of ranibizumab, 0.5 mg and 2.0 mg, administered monthly or on an as-needed basis over 24 months. Main Outcomes and Measures: Post hoc analyses of flattened PED frequency at month 1, univariate and multivariable analysis of patient and ocular characteristics at baseline and PED status at month 1, and total number of ranibizumab injections received stratified by PED status at month 1. Results: A total of 35.5% of patients (208 of 586) with PED at baseline achieved a flattened PED after a single ranibizumab injection. An additional 17.3% subsequently achieved a flattened PED at month 2. Univariate analysis identified an association between older age, lower PED height, and lower subretinal fluid thickness with PED flattening after a single injection. Multivariable analysis identified PED height as a factor associated with this anatomical outcome. Best-corrected visual acuity scores were not superior based on PED flattening at month 1. On average, patients in the as-needed arm who achieved a flattened PED after a single ranibizumab injection required fewer injections by month 24 vs patients whose PED remained present at month 1 (11.0 vs 14.2; difference, 3.3; 95% CI, 1.9-4.6; P < .001). Conclusions and Relevance: In this group of treatment-naive patients with PED from nAMD, after the initial ranibizumab injection approximately one-third and after the second injection approximately one-half had flattened PEDS, although visual outcomes were not superior among those that did vs did not have flattening. The findings suggest flattening may serve as a marker for less intensive as-needed injection frequencies. Trial Registration: ClinicalTrials.gov Identifier: NCT00891735.

ATYPICAL PERIPAPILLARY INNER RETINOSCHISIS IN STELLATE NONHEREDITARY IDIOPATHIC FOVEOMACULAR RETINOSCHISIS.

PURPOSE: To describe an atypical presentation of a patient with stellate nonhereditary idiopathic foveomacular retinoschisis with peripapillary retinoschisis of multiple layers. METHODS: Complete ophthalmic examination including dilated extended ophthalmoscopy, fluorescein angiography, optical coherence tomography, optical coherence tomography angiography, and wide-field fundus photography. RESULTS: A 36-year-old Chinese American woman with mild myopia and good visual acuity (20/20) exhibited macular splitting of the outer plexiform layer on spectral domain optical coherence tomography with an attached hyaloid in her left eye. Peripheral spectral domain optical coherence tomography also demonstrated peripapillary and midperipheral inner retinoschisis, involving the outer plexiform layer and inner retina. The right eye was unremarkable. The diagnosis of stellate nonhereditary idiopathic foveomacular retinoschisis was made because of a lack of other associated ocular conditions and no family history of retinoschisis. CONCLUSION: Stellate nonhereditary idiopathic foveomacular retinoschisis is a recently described and uncommon cause of foveomacular retinoschisis in myopic women with good visual acuity. Recent evidence suggests that peripheral imaging is key in identifying other findings, including midperipheral or peripapillary inner retinoschisis, involving the outer plexiform layer and the inner retina. Our patient may represent a variant of stellate nonhereditary idiopathic foveomacular retinoschisis that can be characterized by multilayer peripapillary retinoschisis.

Angiofibrotic response to vascular endothelial growth factor inhibition in diabetic retinal detachment: report no. 1.

OBJECTIVES To assess the effect of bevacizumab injection on connective tissue growth factor (CTGF) and vascular endothelial growth factor (VEGF) in the ocular fluids of patients with diabetic traction retinal detachment, and to determine whether intraoperative and postoperative complications are decreased in eyes given adjunctive preoperative bevacizumab injection. METHODS Twenty eyes of 19 patients were randomized to receive intravitreal bevacizumab or sham injection 3 to 7 days before vitrectomy for severe proliferative diabetic retinopathy. We collected aqueous samples before injection and at the time of vitrectomy and extracted undiluted vitreous samples. RESULTS Five eyes had decreased vascularization of membranes from preinjection to the time of vitrectomy (all in the bevacizumab treatment arm). Median visual acuities were 20/400 in control eyes at baseline and postoperative month 3 (POM3) and 8/200 in the bevacizumab-treated group at baseline and 20/100 at POM3 (P= .30 between control and bevacizumab-treated groups at POM3). All retinas were attached at POM3. Vitreous levels of VEGF were significantly lower in the bevacizumab group than in the control group (P= .03). Vitreous levels of CTGF were slightly lower in the bevacizumab group compared with the control group, but this difference was not statistically significant (P= .38). Levels of CTGF in the aqueous were strongly correlated with CTGF levels in the vitreous of controls (Spearman correlation coefficient, 0.95 [P< .001]). CONCLUSIONS Intravitreal bevacizumab injection reduces vitreous levels of VEGF and produces a clinically observable alteration in diabetic fibrovascular membranes. Ocular fluid levels of CTGF are not significantly affected within the week after VEGF inhibition. Retinal reattachment rates and visual acuity are not significantly altered by preoperative intravitreal bevacizumab injection at POM3. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT01270542.

Optical coherence tomography findings in paraneoplastic pseudovitelliform lesions in melanoma-associated retinopathy.

PURPOSE: To report an unusual case of paraneoplastic pseudovitelliform lesions associated with melanoma-associated retinopathy (MAR). DESIGN: Observational case report. METHODS: Retrospective review of the ophthalmic examination, fundus photography, fluorescein angiography, electroretinogram (ERG), and optical coherence tomography (OCT) of a patient with MAR. RESULTS: A 65-year-old Caucasian man with a two-year history of metastatic melanoma was referred for evaluation of a six-month history of nyctalopia. Funduscopic examination in both eyes revealed multiple, creamy, yellow, pseudovitelliform lesions in the posterior pole, varying in size from 100-500 mum, at the level of the outer retinal/retinal pigment epithelium (RPE) junction, coalescing along the inferior portion, with overlying macular neurosensory detachments. OCT showed bilateral macular neurosensory detachments with multiple small areas of high reflectivity at the level of the outer retinal/RPE junction. ERG demonstrated a selective loss of the b-wave and a normal a-wave under dark adapted, scotopic conditions. CONCLUSION: Clinicians should be aware of this atypical presentation of MAR that may include pseudovitelliform retinal findings.

Conjunctival epithelium in pars plana vitrectomy specimens.

PURPOSE: To review histopathology of vitrectomy specimens obtained during routine pars plana vitrectomy (PPV) for evidence of inadvertent introduction of conjunctival epithelium into the vitreous cavity during PPV. METHODS: Retrospective review of all vitreous specimens obtained from PPV over a 3-year period during which vitreous samples were routinely submitted from routine and diagnostic PPV. Patient charts and operative reports were reviewed, with particular attention to history of postoperative endophthalmitis, and the use of transconjunctival PPV. RESULTS: A total of 650 specimens were obtained over a 3-year period. Three specimens with conjunctival epithelium were identified. None of these cases resulted in endophthalmitis. Two of these three cases used transconjunctival techniques. In one case all three sclerotomies were made using transconjunctival techniques. CONCLUSIONS: The presence of conjunctiva in the vitreous aspirate from completely transconjunctival PPV indicates that conjunctival epithelium can be inadvertently introduced into the vitreous cavity during PPV. Although none of these cases resulted in endophthalmitis, special care to sterilize the conjunctiva before the creation of transconjunctival sclerotomies is warranted.

Effect of oxygenated intraocular irrigation solutions on the electroretinogram after vitrectomy.

PURPOSE: To investigate the effect of oxygenated intraocular irrigating solutions on electroretinograms (ERGs) for postvitrectomy rabbits. METHODS: Eight groups of five rabbits each underwent pars plana vitrectomy on the right eye; the left eye of each rabbit served as control. The intraocular irrigating solutions were balanced salt solution (BSS), BSS-plus, BSS + oxygen (BSS + O2), BSS-plus + O2, and combinations of each with the addition of endoillumination (L). All animals were evaluated by single-flash scotopic electroretinography on the operated and nonoperated eyes before surgery and at 1 hour, 1 day, 1 week, and 1 month after surgery by an unmasked observer. The main outcome measures were dark-adapted b-wave amplitudes of operated eye/nonoperated eye ratios. The results for the different groups were compared by analysis of variance. RESULTS: Mean dark-adapted b-wave amplitudes of operated eye/nonoperated eye ratios +/- SD for BSS-plus and BSS-plus + O2 before surgery and 1 hour, 1 day, 1 week, and 1 month after surgery were 1.01 +/- 0.09, 0.50 +/- 0.11, 0.95 +/- 0.11, 0.97 +/- 0.11, and 0.99 +/- 0.08 and 0.98 +/- 0.08, 0.59 +/- 0.10, 0.92 +/- 0.06, 0.97 +/- 0.08, and 0.97 +/- 0.10, respectively. At both 1 hour and 1 day after surgery, rabbits treated with BSS-plus + O2 had an earlier b-wave return to baseline findings, but the differences were not statistically significant (P > 0.05). Mean dark-adapted b-wave amplitudes of operated eye/nonoperated eye ratios +/- SD for BSS and BSS + O2 before surgery and 1 hour, 1 day, 1 week, and 1 month after surgery were 1.02 +/- 0.10, 0.47 +/- 0.09, 0.77 +/- 0.07, 0.89 +/- 0.07, and 0.89 +/- 0.07 and 1.02 +/- 0.06, 0.62 +/- 0.16, 0.94 +/- 0.09, 0.97 +/- 0.08, and 0.96 +/- 0.06, respectively. One hour and 1 day after surgery, ERG readings for rabbits treated with BSS + O2 exhibited a statistically significantly earlier return of ERG voltage to baseline values compared with both BSS and BSS + L (P = 0.05 and P = 0.02, respectively). One day after surgery, rabbits treated with BSS alone had the lowest ERG ratios. One week and 1 month after surgery, for all solutions tested other than BSS, ERG values were within normal limits. CONCLUSION: The use of oxygenated solutions appears to affect ERG readings after pars plana vitrectomy. Further studies to evaluate the role of oxygenated solutions in different vitreoretinal surgical procedures are warranted.

Retinal prostheses for the blind.

INTRODUCTION: Using artificial means to treat extreme vision impairment has come closer to reality during the past few decades. The goal of this research has been to create an implantable medical device that provides useful vision for those patients who are left with no alternatives. Analogous to the cochlear implants for some forms of hearing loss, these devices could restore useful vision by converting visual information into patterns of electrical stimulation that excite the remaining viable inner retinal neurons in patients with retinitis pigmentosa or age-related macular degeneration. METHODS: Data for this review were selected through a comprehensive literature search. RESULTS: Advances in microtechnology have facilitated the development of a variety of prostheses that can be implanted in the visual cortex, around the optic nerve, or in the eye. Some of these approaches have shown the promise of providing useful visual input to patients with visual impairments. CONCLUSION: While the development of various retinal prostheses have shown promise in limited clinical trials, there are distinct advantages and disadvantages for each type of prosthesis. This review will focus primarily on the Epiretinal Intraocular Retinal Prosthesis, studied by our group, but will also briefly review other modalities: the subretinal prosthesis, cortical prosthesis, and optic nerve prosthesis.

Outcomes of 140 consecutive cases of 25-gauge transconjunctival surgery for posterior segment disease.

PURPOSE: To evaluate the safety and efficacy of 25-gauge instrumentation for a variety of vitreoretinal conditions on previously nonvitrectomized eyes. DESIGN: Single-center, retrospective, interventional case series. PARTICIPANTS: One-hundred forty eyes of 140 patients were evaluated at the Doheny Retina Institute from July 2002 to July 2003. INTERVENTION: All patients underwent surgical procedures using the Millennium 25-gauge Transconjunctival Standard Vitrectomy system. Twenty eyes (14.3%) underwent procedures without vitrectomy. MAIN OUTCOME MEASURES: Postoperative visual acuity (VA), intraocular pressure, surgical time, postoperative inflammation, complications, and number of sutured sites. RESULTS: No intraoperative complications were noted. No cases required conversion to 20-gauge machines. Ten cases (7.1%) involved single-site sclerotomy suture placement due to bleb formation at the conclusion of the procedure, but 5 of these entry sites were enlarged to facilitate larger instrumentation for tissue manipulation. Median VA improved from 20/250 (logarithm of the minimum angle of resolution, 1.08+/-0.47) preoperatively to 20/60 (0.47+/-0.30) (P<0.0001) at final visit. Mean follow-up was 33.8+/-9.7 weeks, and all eyes were observed for a minimum of 12 weeks. Mean total surgical time was 17.4+/-6.9 minutes. Intraocular pressures remained stable throughout the postoperative course. Five eyes (3.8%) presented on day 1 with shallow choroidal detachments, but all resolved by day 7, and none required volume infusion during the postoperative period. All but one of these cases was within the first 50 procedures performed. No detectable inflammation was noted in any eyes by 4 weeks postoperatively. No case of retinal detachment or endophthalmitis was recorded. CONCLUSIONS: Transconjunctival surgery using 25-gauge instrumentation may hasten postoperative recovery by decreasing overall surgical time and postoperative inflammation. Procedures requiring minimal intraocular manipulation did not require sutures and, thus, may be better suited for this surgical modality.

Transvitreal limited arteriovenous-crossing manipulation without vitrectomy for complicated branch retinal vein occlusion using 25-gauge instrumentation.

PURPOSE: To evaluate a new technique, 25-gauge transvitreal limited arteriovenous-crossing manipulation without vitrectomy (LAM), for the treatment of branch retinal vein occlusion (BRVO) complicated by macular hemorrhage and/or macular edema recalcitrant to grid laser photocoagulation. METHODS: Twelve eyes of 12 patients underwent LAM for BRVO performed by a single surgeon (M.S.H.) using the 25-gauge nitinol flexible-extendable blunt pick. The presence or absence of intraoperative reperfusion visualization, pre- and postoperative visual acuity, macular thickness as measured by optical coherence tomography, intraocular pressure, and lens status were evaluated. RESULTS: Restoration of blood flow was noted in all patients and was based on intraoperative reestablishment of a red column of erythrocytes through the previously closed vessel. Mean visual acuity improved from 20/200 (logarithm of the minimal angle of resolution [LogMAR] +/- SD, 1.00 +/- 0.32) preoperatively to 20/70 (LogMAR +/- SD, 0.56 +/- 0.28) (P = 0.0003) at the final visit. Eleven (92%) of 12 eyes had >or=2 lines of visual improvement. Five eyes (45%) had final visual acuity of 20/50 or better. Mean macular thickness +/- SD improved from 401.0 +/- 73.2 to 178.7 +/- 19.6 microm (P < 0.0001) at the final visit. No statistically significant difference was noted in cataract progression or intraocular pressure. Mean follow-up +/- SD was 49.9 +/- 19.6 weeks. All patients were observed for at least 12 weeks. CONCLUSION: LAM may achieve outcomes comparable with those of arteriovenous adventitial sheathotomy for complicated BRVO.

Retinal thickness in normal and RCD1 dogs using optical coherence tomography.

BACKGROUND AND OBJECTIVE: To compare retinal thickness and retinal nerve fiber layer (RNFL) thickness values obtained by optical coherence tomography (OCT) in normal dogs and dogs with rod-cone dysplasia type 1 (RCD1). MATERIALS AND METHODS: Eight eyes of 6 normal hound-bred dogs and 12 eyes of 6 dogs with RCD1, 2 to 5 years of age, were examined using the Fast RNFL Thickness, Fast Macular Thickness, and line scan protocols of OCT. RESULTS: Retinal thickness was significantly higher in the tapetal fundus than in the non-tapetal fundus, in both normal (P = .0036) and RCD1 (P < .0001) dogs. Superotemporal, superonasal, and inferior retinal thickness values were significantly higher in normal dogs (P < .0001). Area centralis thickness was 183.5 +/- 10.66 microm in normal dogs and 136.16 +/- 13.12 microm in RCD1 dogs (P < .0001). There was no difference in RNFL thickness between normal and RCD1 dogs (P > .05). CONCLUSION: OCT scanning in dogs is considered to be a useful method of evaluation in future retinal studies in this animal model.

Retinal vein cannulation with prolonged infusion of tissue plasminogen activator (t-PA) for the treatment of experimental retinal vein occlusion in dogs.

PURPOSE: To evaluate the feasibility, safety, and efficacy of local thrombolytic agents directly injected into occluded retinal veins in an experimental animal model. DESIGN: Experimental animal study. METHODS: This experimental study was performed in two phases. In phase 1, 15 enucleated porcine eyes and 8 in vivo canine eyes were used for the development of the instrumentation and surgical technique required for retinal vein cannulation with prolonged intravascular infusion. In phase 2 of this study, experimental branch retinal vein occlusion was photo-chemically created using an intravenous injection of rose bengal followed by diode laser photocoagulation in eight eyes of eight dogs. Four eyes were treated by retinal vein cannulation and an injection of tissue plasminogen activator (t-PA) using a specifically designed microcatheter, while the remaining four eyes were untreated (control group). The total amount of t-PA injected intravenously ranged from 400 to 1000 mug, infused over a period ranging from 25 to 45 minutes with a mean pressure of 40 psi, resulting in a mean injection flow rate of 0.05 ml/min. The dogs underwent clinical examination, fluorescein angiography, and histologic examination. Main outcome measures were: Achievement of prolonged intravascular infusion of t-PA, changes in fundus appearance, fluorescein angiography, and histology. RESULTS: A microcatheter instrument and a surgical technique for retinal vein cannulation with prolonged intravascular infusion were developed. Cannulation and t-PA infusion for a period of at least 30 minutes was achieved in all four treated eyes with experimental branch retinal vein occlusion. No complications were recorded in all treated eyes. One week and 1 month postoperatively, treated eyes exhibited marked decreases in retinal hemorrhages, retinal vein dilation, and tortuosity, whereas nontreated eyes exhibited persistence of these findings. Fluorescein angiography demonstrated improved circulatory flow in treated relative to nontreated eyes. Histologic analysis confirmed the presence of thrombi in nontreated eyes only. CONCLUSIONS: Retinal vein cannulation with prolonged intravascular injection of t-PA is feasible and safe, and this may offer a new treatment option for retinal vein occlusion.