Analysis of ophthalmology subspecialty opioid prescribing patterns during the opioid public health crisis.

OBJECTIVE: To describe opioid prescribing practices of ophthalmology subspecialties and determine whether opioid prescribing has decreased during the public health crisis. DESIGN: Retrospective cohort study. PARTICIPANTS: Ophthalmologists prescribing at least 11 medications billed to the Medicare Part D prescription drug plan. METHODS: Publicly available Medicare data sets based on claims from the years 2016, 2017, and 2018 were used. Fellowship status was assumed based on subspecialty society membership or use of specified Current Procedural Terminology codes. The main outcome was the percentage of physicians in each subspecialty prescribing opioids. RESULTS: The database included 19,762, 19,790, and 19,840 ophthalmologists in the years 2016, 2017, and 2018, respectively. Only the subspecialties of comprehensive ophthalmology (43.5% vs 39.6% vs 35.7%; p < 0.001; φc = 0.066), retina (66.5% vs 60.7% vs 54.5%; p < 0.001; φc = 0.101), cornea (82.8% vs 83.9% vs 77.2%; p = 0.03; φc = 0.076), and glaucoma (53.4% vs 46.4% vs 42.0%; p < 0.001; φc = 0.094) underwent a small but significant reduction in the proportion of physicians prescribing opioids. The subspecialties of oculoplastics (86%-88.8%), cornea (77.2%-82.8%), retina (54.5%-66.5%), and pediatrics (51.5%-57.9%) had the highest percentage of physicians prescribing opioids. The subspecialties of glaucoma, uveitis, and comprehensive ophthalmology had the lowest percentage of opioid prescribers. Among physicians with more than 10 opioid claims, median opioid claims did not change drastically. Opioids contributed only a small proportion of medication claims for all subspecialties. CONCLUSION: All subspecialties experienced either a small reduction or no significant change in the percentage of opioid prescribers during the period analyzed. We hope to encourage collaboration between ophthalmology subspecialties in striving to reduce opioid prescribing. Further studies are needed to better fine-tune opioid prescribing practices.

TOXOPLASMOSIS RETINOCHOROIDITIS MASQUERADING AS ENDOGENOUS ENDOPHTHALMITIS IN A CASE OF CONGENITAL LONG QT SYNDROME.

PURPOSE: To describe the diagnostic and treatment challenges of a case of presumed acquired macula-involving toxoplasmosis retinochoroiditis. METHODS: Case report of a woman with congenital long QT syndrome presenting with retinochoroiditis after undergoing a cardiac procedure. Laboratory analysis, ocular fluid biopsy, and multimodal imaging were obtained. RESULTS: Ophthalmic examination was significant for decreased vision and a macula-involving chorioretinal lesion concerning for endogenous endophthalmitis. Multimodal imaging showed a focal, full-thickness necrotizing process associated with vitritis, retinal edema, and choroidal thickening. Analysis of peripheral blood revealed elevated serum toxoplasma Immunoglobulin G titers. Blood cultures and a transesophageal echocardiogram were negative for endocarditis. Aqueous and vitreous specimens were negative for an infectious polymerase chain reaction panel, including toxoplasmosis and negative bacterial and fungal cultures. A diagnosis of presumed acquired toxoplasmosis retinochoroiditis was made and treated with a combination of oral and intravitreal antiparasitic medications resulting in healing of the retinochoroiditis. CONCLUSION: To the authors' knowledge, this is the first reported case of acquired toxoplasmosis retinochoroiditis in an immunocompetent patient with congenital long QT syndrome masquerading as endogenous endophthalmitis. The association of congenital long QT syndrome and a recent cardiac procedure with a risk for endogenous endophthalmitis complicated the diagnosis, clinical course, and treatment options. Our case emphasizes the importance of a thorough patient history, comprehensive clinical examination, and supportive multimodal imaging that were used to characterize the infectious process and guide empirical treatment. In addition, laboratory analysis, comanagement with other specialists, and evaluating the response to antitoxoplasma therapy were all instrumental in the eventual diagnosis and treatment of ocular toxoplasmosis in this atypical case.

DARK WITHOUT PRESSURE IN A CASE OF CHOROIDAL OSTEOMA.

PURPOSE: To report a novel case of dark without pressure in a patient with a choroidal osteoma. To our knowledge, this association has not been previously reported. METHODS: Observational case report. Review of clinical examination and multi-modal imaging findings in a patient with a choroidal osteoma and dark without pressure. RESULTS: A 21-year-old African American woman with no significant past medical history presented with a large, unilateral, juxtapapillary, subretinal, orange-colored, ovoid-shaped lesion with macular involvement. An overlying area of mottled pigmentary changes, fibrosis, and atrophy were present. Adjacent to and surrounding the osteoma was an annular band of hyperpigmented mid-peripheral retina with a sharply demarcated scalloped border that abruptly changed to normal-appearing peripheral retina. Multi-modal imaging including wide-field fluorescein angiography, optical coherence tomography, and ophthalmic B-scan were performed. The funduscopic and imaging findings were consistent with a diagnosis of choroidal osteoma and dark without pressure. CONCLUSION: The examination and imaging findings in this patient suggest a unique association between two relatively uncommon lesions, choroidal osteoma, and dark without pressure. Although these two lesions may simply be coinciding in the same eye, there may be an association with space-occupying lesions causing a change in photoreceptor structure.

Comparison of Povidone-Iodine and Gentamicin Soak as Scleral Buckle Infection Prophylaxis.

OBJECTIVE: To determine the best method of antimicrobial prophylaxis against implanted material-associated infections in the setting of scleral buckle surgery. DESIGN: Experimental study. PARTICIPANTS: Scleral buckle elements were soaked in either gram-positive or polymicrobial broth, while control buckle elements were soaked in PBS only. METHODS: Solid silicone and sponge scleral buckle elements were inoculated with common pathogens of the ocular surface, and then soaked in either 1% or 5% povidone-iodine, 1 mg/mL gentamicin solution, or sterile saline for 1, 5, 10, or 15 minutes. Bacteria were then isolated from the buckle elements and cultured for 24 hours. RESULTS: In all gram-positive bacterial conditions, gentamicin solution decreased the bacterial load from 451,666.67 colony-forming units (CFU)/mL to 171,611.11 CFU/mL (p=0.0004). The fractional bacterial survival after soaking in gentamicin was higher for the silicone sponge than band (0.357 vs 0.079, p=0.038). Both 1% and 5% povidone-iodine were able to completely eradicate all gram-positive bacteria of both buckle elements. Only 5% povidone-iodine was able to completely sterilize all microbes on the buckle after soaking in a polymicrobial solution consisting of gram-positive, gram-negative bacteria, and fungi. CONCLUSION: Povidone-iodine solution was significantly more effective at bacterial eradication compared to gentamicin solution. For all scleral buckle procedures, we recommend soaking the buckle element in 2-3% povidone-iodine solution before placement and rinsing the ocular surface with the same solution after placement.

RETINAL TELANGIECTASIA ASSOCIATED WITH OPTIC DISK PIT MACULOPATHY.

PURPOSE: To report a case of optic pit maculopathy with retinoschisis-like edema with a rare finding of retinal telangiectasia. METHODS: Retrospective case report. RESULTS: A 22-year-old white man with a right optic pit presented with blurry vision and was found to have optic pit maculopathy with retinoschisis-like macular edema and retinal telangiectasia along the superior-temporal arcade. The patient underwent pars plana vitrectomy with separation of posterior vitreous and inner retinal fenestration. Upon follow-up, retinal telangiectasia was resolved and retinoschisis-like edema was mostly resolved 2 years after surgery. CONCLUSION: Retinal telangiectasia seen in optic disk maculopathy may be secondary to ischemia induced by the intense stretching of the superficial vascular plexus in the inner retina because of macular edema. In our patient, when traction was relieved following surgical intervention, there was remodeling of the superficial vascular plexus that allowed for resolution of the retinal telangiectasia.

Comparison of AAV-Mediated Optogenetic Vision Restoration between Retinal Ganglion Cell Expression and ON Bipolar Cell Targeting.

The loss of photoreceptors in individuals with retinal degenerative diseases leads to partial or complete blindness. Optogenetic therapy is a promising approach for restoring vision to the blind. Multiple strategies have been employed by targeting genetically encoded light sensors, particularly channelrhodopsins, to surviving retinal neurons in animal models. In particular, the strategy of targeting retinal bipolar cells has commonly been expected to result in better vision than ubiquitous expression in retinal ganglion cells. However, a direct comparison of the channelrhodopsin-restored vision between these two strategies has not been performed. Here, we compared the restored visual functions achieved by adeno-associated virus (AAV)-mediated expression of a channelrhodopsin in ON-type bipolar cells and retinal ganglion cells driven by an improved mGluR6 promoter and a CAG promoter, respectively, in a blind mouse model by performing electrophysiological recordings and behavioral assessments. Unexpectedly, the efficacy of the restored vision based on light sensitivity and visual acuity was much higher following ubiquitous retinal ganglion cell expression than that of the strategy targeting ON-type bipolar cells. Our study suggests that, at least based on currently available gene delivery techniques, the expression of genetically encoded light sensors in retinal ganglion cells is likely a practical and advantageous strategy for optogenetic vision restoration.

Effect of Proteasome Inhibitors on the AAV-Mediated Transduction Efficiency in Retinal Bipolar Cells.

BACKGROUND: Adeno-associated Virus (AAV) vectors are the most promising vehicles for therapeutic gene delivery to the retina. To develop a practical gene delivery tool, achieving high AAV transduction efficiency in specific cell types is often required. AAV-mediated targeted expression in retinal bipolar cells is needed in certain applications such as optogenetic therapy, however, the transduction efficiency driven by endogenous cell-specific promoters is usually low. Methods that can improve AAV transduction efficiency in bipolar cells need to be developed. OBJECTIVE: The study aimed to examine the effect of proteasome inhibitors on AAV-mediated transduction efficiency in retinal bipolar cells. METHODS: Quantitative analysis of fluorescent reporter protein expression was performed to assess the effect of two proteasome inhibitors, doxorubicin and MG132, on AAV-mediated transduction efficiency in retinal bipolar cells in mice. RESULTS: Our results showed that doxorubicin can increase the AAV transduction efficiency in retinal bipolar cells in a dose-dependent manner. We also observed doxorubicin-mediated cytotoxicity in retinal neurons, but the cytotoxicity could be mitigated by the coapplication of dexrazoxane. Three months after the coapplication of doxorubicin (300 µM) and dexrazoxane, the AAV transduction efficiency in retinal bipolar cells increased by 33.8% and no cytotoxicity was observed in all the layers of the retina. CONCLUSION: Doxorubicin could enhance the AAV transduction efficiency in retinal bipolar cells in vivo. The potential long-term cytotoxicity caused by doxorubicin to retinal neurons could be partially mitigated by dexrazoxane. The coapplication of doxorubicin and dexrazoxane may serve as a potential adjuvant regimen for improving AAV transduction efficiency in retinal bipolar cells.

INDUCIBLE TRANSIENT CENTRAL RETINAL ARTERY VASOSPASM: A CASE REPORT.

PURPOSE: To report a case of inducible transient central retinal artery vasospasm with associated imaging. METHODS: Observational case report. RESULTS: A 51-year-old man presented for outpatient follow-up for recurrent inducible transient vision loss in his right eye. He experienced an episode during examination and was found to have central retinal artery vasospasm. Fundus photography and fluorescein angiography obtained during his vasospastic attack confirmed retinal arterial vasospasm. Treatment with a calcium-channel blocker (nifedipine) has been effective in preventing recurrent attacks. CONCLUSION: Idiopathic primary vasospasm is a rare cause of transient vision loss that is difficult to confirm because of the transient nature. We obtained imaging showing the initiation and resolution of the vasospastic event. The patient was then successfully treated with a calcium-channel blocker.

Epigenetic Modifications in Peripheral Blood as Potential Noninvasive Biomarker of Diabetic Retinopathy.

PURPOSE: Progression of diabetic retinopathy is related to the duration and severity of hyperglycemia, and after 25 years of diabetes, 90% of patients show some signs of retinopathy. Despite initiation of many retinal molecular/biochemical abnormalities, including mitochondrial damage and epigenetic modifications, the disease remains asympotomatic in the initial stages. Our goal is to examine the utility of DNA methylation as a possible biomarker of diabetic retinopathy. METHODS: Genomic DNA (gDNA) was isolated from the buffy coat, isolated from blood of diabetic patients with proliferative (PDR) or no retinopathy (No-DR), and nondiabetic subjects (CONT). Methylation of mitochondrial DNA (mtDNA), especially its D-Loop (the site of mtDNA transcription/replication), was quantified by methylated DNA immunoprecipitation and methyl-specific PCR techniques. Results were confirmed in purified mtDNA. The specific D-Loop region with the highest DNA methylation was identified using five overlapping primers, and DNMT1 binding was quantified by chromatin immunoprecipitation. Promoter DNA methylation of DNA mismatch repair (MLH1) and superoxide scavenging (SOD2) enzymes were also quantified. RESULTS: Compared to CONT, D-Loop methylation was higher in PDR and No-DR groups, and the D-Loop region responsible for encoding the majority of the mtDNA-encoded genes had significantly higher methylation in the PDR group versus No-DR. Similarly, compared to No-DR, the PDR group also had hypermethylated MHL1 and SOD2 promoters. CONCLUSIONS: Blood from PDR patients have higher DNA methylation, than seen in diabetic patients without retinopathy. Thus, DNA methylation can be used as a possible biomarker of diabetic retinopathy. TRANSLATIONAL RELEVANCE: DNA methylation status in the blood of diabetic patients could serve as a potential noninvasive biomarker of retinopathy, and also an important readout parameter for testing longitudinal outcome of novel therapeutics for this blinding disease.

Improved CoChR Variants Restore Visual Acuity and Contrast Sensitivity in a Mouse Model of Blindness under Ambient Light Conditions.

Severe photoreceptor cell death in retinal degenerative diseases leads to partial or complete blindness. Optogenetics is a promising strategy to treat blindness. The feasibility of this strategy has been demonstrated through the ectopic expression of microbial channelrhodopsins (ChRs) and other genetically encoded light sensors in surviving retinal neurons in animal models. A major drawback for ChR-based visual restoration is low light sensitivity. Here, we report the development of highly operational light-sensitive ChRs by optimizing the kinetics of a recently reported ChR variant, Chloromonas oogama (CoChR). In particular, we identified two CoChR mutants, CoChR-L112C and CoChR-H94E/L112C/K264T, with markedly enhanced light sensitivity. The improved light sensitivity of the CoChR mutants was confirmed by ex vivo electrophysiological recordings in the retina. Furthermore, the CoChR mutants restored the vision of a blind mouse model under ambient light conditions with remarkably good contrast sensitivity and visual acuity, as evidenced by the results of behavioral assays. The ability to restore functional vision under normal light conditions with the improved CoChR variants removed a major obstacle for ChR-based optogenetic vision restoration.

RETINAL AND CHOROIDAL VASCULAR OCCLUSION FOLLOWING AQUEOUS MISDIRECTION SYNDROME IN A PATIENT WITH SICKLE CELL TRAIT.

PURPOSE: To report a patient with retinal and choroidal vascular occlusion as a presenting sign of sickle cell trait following the development of aqueous misdirection syndrome. METHODS: Retrospective chart review. RESULTS: A patient treated for bilateral chronic angle-closure glaucoma with sequential EX-PRESS glaucoma filtration device surgery developed sequential bilateral aqueous misdirection syndrome. The left eye developed retinal arterial and localized choroidal vascular occlusions subsequent to an acute elevation in intraocular pressure and possibly the use of oral acetazolamide. The patient was subsequently found to have sickle cell trait. The right eye developed aqueous misdirection with acute elevation of intraocular pressure as well, but the patient was not treated with oral acetazolamide and did not develop vascular occlusion. CONCLUSION: Retinal and choroidal vascular occlusions can be the presenting sign of a patient with sickle cell trait. Sickle cell screening may be beneficial in African American or Middle Eastern patients after an acute rise in intraocular pressure, particularly before initiation of treatment with oral carbonic anhydrase inhibitors.

A Robust Optomotor Assay for Assessing the Efficacy of Optogenetic Tools for Vision Restoration.

Purpose: To develop an animal behavioral assay for the quantitative assessment of the functional efficacy of optogenetic therapies. Methods: A triple-knockout (TKO) mouse line, Gnat1-/-Cnga3-/-Opn4-/-, and a double-knockout mouse line, Gnat1-/-Cnga3-/-, were employed. The expression of channelrhodopsin-2 (ChR2) and its three more light-sensitive mutants, ChR2-L132C, ChR2-L132C/T159C, and ChR2-132C/T159S, in inner retinal neurons was achieved using rAAV2 vectors via intravitreal delivery. Pupillary constriction was assessed by measuring the pupil diameter. The optomotor response (OMR) was examined using a homemade optomotor system equipped with light-emitting diodes as light stimulation. Results: A robust OMR was restored in the ChR2-mutant-expressing TKO mice; however, significant pupillary constriction was observed only for the ChR2-L132C/T159S mutant. The ability to evoke an OMR was dependent on both the light intensity and grating frequency. The most light-sensitive frequency for the three ChR2 mutants was approximately 0.042 cycles per degree. Among the three ChR2 mutants, ChR2-L132C/T159S was the most light sensitive, followed by ChR2-L132C/T159C and ChR2-L132C. Melanopsin-mediated pupillary constriction resulted in a substantial reduction in the light sensitivity of the ChR2-mediated OMR. Conclusions: The OMR assay using TKO mice enabled the quantitative assessment of the efficacy of different optogenetic tools and the properties of optogenetically restored vision. Thus, the assay can serve as a valuable tool for developing effective optogenetic therapies.

OUTCOMES OF REPEAT PARS PLANA VITRECTOMY AFTER FAILED SURGERY FOR PROLIFERATIVE VITREORETINOPATHY.

PURPOSE: To evaluate outcomes of repeat pars plana vitrectomy for proliferative vitreoretinopathy after previous failed pars plana vitrectomy. METHODS: This is a retrospective case series including 51 eyes of 50 patients who underwent repeat surgery after failed previous pars plana vitrectomy for proliferative vitreoretinopathy from 2000 to 2015 at the Kresge Eye Institute, Detroit, MI. Patients were classified into successful and unsuccessful groups. Success was defined as retinal reattachment, silicone oil removed, and best-corrected visual acuity (BCVA) ≥5/200 at the final follow-up visit. RESULTS: Forty-three eyes (84.3%) were successfully reattached at the last follow-up. Seventeen (33.3%) eyes were deemed successful and 34 (66.7%) eyes unsuccessful according to our criteria. Compared with the successful group, eyes in the unsuccessful group had more eyes with preoperative BCVA <5/200 (P < 0.001), preoperative BCVA of hand motion or worse (P = 0.002), preoperative flare ≥Grade 2+ (P = 0.03), preoperative posterior breaks (P = 0.02), previous retinectomy (P = 0.04), and final postoperative hypotony (intraocular pressure ≤ 5 mmHg) (P = 0.005). Eyes with silicone oil removed were more likely to have BCVA ≥5/200 (P < 0.001) at the final follow-up visit. Location of patients >100 miles (P = 0.04) from Detroit and preoperative BCVA of hand motion or worse (P = 0.01) were significantly associated with failure in the logistic regression analysis. CONCLUSION: Success after repeat surgery for proliferative vitreoretinopathy should include ambulatory vision, retinal reattachment, and silicone oil removal. We identified several preoperative and perioperative factors that were associated with success in the bivariate and logistic analyses. The decision to perform surgical reoperation in these patients should be based on multiple factors, most importantly preoperative BCVA.

Assessment of Neurotrophins and Inflammatory Mediators in Vitreous of Patients With Diabetic Retinopathy.

Purpose: To assess vitreous levels of inflammatory cytokines and neurotrophins (NTs) in diabetic retinopathy (DR) and elucidate their potential roles. Methods: A prospective study was performed on 50 vitreous samples obtained from patients with DR (n = 22) and the nondiabetic controls (n = 28). All patients were candidates for vitrectomy. Inflammatory cytokine and NT levels were determined with ELISA. Potential source and role of NTs was determined by using human retinal Müller glia and mouse photoreceptor cells and challenging them with TNF-α or IL-1ß, followed by detection of NTs and cell death. Results: Vitreous NT levels of all DR patients were significantly higher than those of nondiabetic controls (nerve growth factor [NGF, P = 0.0001], brain-derived neurotrophic factor [BDNF, P = 0.009], neurotrophin-3 [NT-3, P < 0.0001], neurotrophin-4 [NT-4, P = 0.0001], ciliary neurotrophic factor [CNTF, P = 0.0001], and glial cell-derived neurotrophic factor [GDNF, P = 0.008]). Similarly, the levels of inflammatory mediators IL-1ß (P < 0.0001), IL-6 (P = 0.0005), IL-8 (P < 0.0001), and TNF-α (P < 0.0001) were also higher in eyes with DR. Interestingly, inflammatory cytokine and NT levels, particularly TNF-α (P < 0.05), IL-8 (P < 0.004), NT-3 (P = 0.012), NGF (P = 0.04), GDNF (P = 0.005), and CNTF (P = 0.002), were higher in eyes with nonproliferative diabetic retinopathy (NPDR) than in eyes with active proliferative diabetic retinopathy (PDR). Cytokine stimulation of Müller glia resulted in production of NTs, and GDNF treatment reduced photoreceptor cell death in response to inflammation and oxidative stress. Conclusions: Together, our study demonstrated that patients with DR have higher levels of both inflammatory cytokines and NTs in their vitreous. Müller glia could be the potential source of NTs under inflammatory conditions to exert neuroprotection.

Zika virus infects cells lining the blood-retinal barrier and causes chorioretinal atrophy in mouse eyes.

Zika virus (ZIKV) is an important pathogen that causes not only neurologic, but also ocular, abnormalities. Thus, it is imperative that models to study ZIKV pathogenesis in the eye are developed to identify potential targets for interventions. Here, we studied ZIKV interactions with human retinal cells and evaluated ZIKV's pathobiology in mouse eyes. We showed that cells lining the blood-retinal barrier (BRB), the retinal endothelium, and retinal pigment epithelium (RPE) were highly permissive and susceptible to ZIKV-induced cell death. Direct inoculation of ZIKV in eyes of adult C57BL/6 and IFN-stimulated gene 15 (ISG15) KO mice caused chorioretinal atrophy with RPE mottling, a common ocular manifestation of congenital ZIKV infection in humans. This response was associated with induced expression of multiple inflammatory and antiviral (IFNs) response genes in the infected mouse retina. Interestingly, ISG15 KO eyes exhibited severe chorioretinitis, which coincided with increased retinal cell death and higher ZIKV replication. Collectively, our study provides the first evidence to our knowledge that ZIKV causes retinal lesions and infects the cells lining the BRB and that ISG15 plays a role in retinal innate defense against ZIKV infection. Our mouse model can be used to study mechanisms underlying ZIKV-induced chorioretinitis and to gauge ocular antiviral therapies.

Functional and Morphological Evaluation of Traumatized Eyes With Berlin's Edema Affecting the Macula Using mfERG, Microperimetry, and SD-OCT.

BACKGROUND AND OBJECTIVE: To describe the structural and functional changes that occur in traumatic Berlin's edema involving the macula through assessment with multifocal electroretinogram (mfERG), microperimetry, fundus photography, and spectral-domain optical coherence tomography (SD-OCT). PATIENTS AND METHODS: Retrospective case series of five eyes from four patients with macular traumatic Berlin's edema. Patients underwent baseline mfERG (three eyes), MP1 microperimetry (three eyes), fundus photography (five eyes), and SD-OCT (five eyes). RESULTS: All eyes with Berlin's edema showed abnormal findings on baseline SD-OCT, including disruption and fragmentation of the inner segment/ outer segment layer. In two patients with unilateral blunt ocular trauma who underwent mfERG, there was complete loss of the foveal peak in affected eyes. All three eyes that underwent microperimetry showed depressed retinal sensitivity in the area of Berlin's edema. CONCLUSION: SD-OCT, microperimetry, and mfERG can be used to help diagnose, stratify traumatic severity, and follow structural and functional progression over time in patients with Berlin's edema. [Ophthalmic Surg Lasers Imaging Retina. 2017;48:114-121.].

Optogenetic Approaches to Restoring Vision.

Severe loss of photoreceptor cells in inherited or acquired retinal degenerative diseases can result in partial loss of sight or complete blindness. The optogenetic strategy for restoration of vision utilizes optogenetic tools to convert surviving inner retinal neurons into photosensitive cells; thus, light sensitivity is imparted to the retina after the death of photoreceptor cells. Proof-of-concept studies, especially those using microbial rhodopsins, have demonstrated restoration of light responses in surviving retinal neurons and visually guided behaviors in animal models. Significant progress has also been made in improving microbial rhodopsin-based optogenetic tools, developing virus-mediated gene delivery, and targeting specific retinal neurons and subcellular compartments of retinal ganglion cells. In this article, we review the current status of the field and outline further directions and challenges to the advancement of this strategy toward clinical application and improvement in the outcomes of restored vision.

Management of retained subretinal perfluorocarbon liquid.

Subretinal perfluorocarbon liquid (PFCL) is a rare but serious complication associated with retinal detachment repair primarily due to the potential for toxic effects of the liquid on various structures of the eye. While it is optimal to detect and remove subretinal PFCL intraoperatively, retained PFCL may be missed in 1% to 11% of cases and not detected until follow-up visits.3,26 In such cases, early intervention appears to be warranted particularly if central vision remains at risk with subfoveally located droplets. Restoration of the foveal contour and attenuation of scotoma size as indicated by optical coherence tomography and microperimetry imaging suggest a good prognosis based on the limited number of case reports reviewed. Prognosis of retained PFCL depends on the location, size, and duration of its contact with retinal structures.

Combined posterior chamber intraocular lens, vitrectomy, Retisert, and pars plana tube in noninfectious uveitis.

OBJECTIVE: To assess the safety and efficacy of combined cataract extraction, posterior chamber intraocular lens placement, pars plana vitrectomy, fluocinolone acetonide intravitreal implant (Retisert), and Ahmed valves with pars plana tube (CPR-PT) in eyes with chronic, posterior, noninfectious uveitis. METHODS: Retrospective study of patients who underwent CPR-PT. Outcome measures included visual acuity, intraocular pressure, inflammation, and complications. RESULTS: Eight eyes were included, with a mean follow-up of 18 months. Mean visual acuity improved from 1.89 to 0.14 logMAR (Snellen, counting fingers at 2 ft [0.6 m]) to 20/30; P=.01). Mean intraocular pressure remained stable at 16 to 17 mm Hg (P=.35). The number of glaucoma medications per eye decreased from 2.9 to 0.25 (P=.01). Systemic prednisone therapy was discontinued in all patients by 9 months postoperatively. Inflammation was well controlled in all eyes. CONCLUSION: The CPR-PT procedure allows rapid visual rehabilitation without major short-term complications.

Intravitreous delivery of the corticosteroid fluocinolone acetonide attenuates retinal degeneration in S334ter-4 rats.

PURPOSE: To study the neuroprotective properties of low-dose, sustained-release intravitreous fluocinolone acetonide (FA) in transgenic S334ter-4 rats. METHODS: S334ter-4 rats aged 4 weeks were divided into four groups: 0.5 microg/d FA-loaded intravitreous drug delivery implant (IDDI); 0.2 microg/d FA-loaded IDDI; inactive IDDI; and unoperated controls. Electroretinography (ERG) was performed before surgery and every 2 weeks after surgery for 8 weeks. When the rats were 12 weeks of age, outer nuclear layer (ONL) and inner nuclear layer (INL) thicknesses were measured. Microglial cell counts were obtained from retinal wholemounts labeled for Iba-1. RESULTS: At the end of the study, unoperated and inactive IDDI-implanted rats demonstrated 50% to 60% reductions in ERG amplitudes compared with those recorded at 4 weeks (P < 0.001 for both groups). FA 0.2-microg/d animals demonstrated 15% amplitude attenuation, while FA 0.5-microg/d animals showed 30% reduction. ONL thickness in FA 0.2-microg/d-treated eyes was 25.8% +/- 2.3% higher than in control group eyes (P < 0.001) and 30.0% +/- 2.1% higher than in inactive IDDI-implanted eyes (P < 0.001). In FA 0.5-microg/d-treated eyes, ONL thickness was 22.4% +/- 2.8% higher than in control group eyes (P < 0.001) and 22.3% +/- 3.7% higher than in inactive IDDI-implanted eyes (P < 0.01). No statistically significant difference was observed between the two control groups. No statistically significant difference between the two FA-treated groups was found. FA-treated groups demonstrated significantly fewer activated microglial cells than control groups. CONCLUSIONS: Chronic intravitreous infusion of FA preserves ONL cell morphology and ERG a- and b-wave amplitudes and reduces retinal neuroinflammation in S334ter rats. Based on these findings, the synthetic corticosteroid FA may promise a therapeutic role in patients with retinal degeneration.