PURPOSE: To describe clinical manifestations, diagnostic approaches, therapy, and outcomes of biopsy-proven intraocular lymphoma. METHODS: Review of tertiary referral center records between 2005 and 2015. RESULTS: A total of 51 eyes of 26 patients were included; mean age of onset was 60.42 years. Common ocular complaints included floaters (42%) and blurred vision (35%); 62% of patients had ocular and central nervous system involvement; 11% had systemic lymphoma; and 27% had only ocular involvement. Vitreous analysis was positive for malignant cells in 77% of patients on initial biopsy, and in 100% of patients on repeat biopsy. In total, 20/26 patients received systemic and topical treatment before IOL diagnosis was made; 25 patients received intravitreal methotrexate and/or rituximab; one patient received intracameral rituximab. All patients achieved remission by their final visit. CONCLUSIONS: Intraocular lymphoma often masquerades as intraocular inflammation, resulting in delayed or misdiagnosis with subsequent inappropriate management. Optimal therapy is a challenge for oncologists and ophthalmologists.

Recent clinical research has highlighted important links between a number of diseases and the tortuosity of curvilinear anatomical structures like corneal nerve fibres, suggesting that tortuosity changes might detect early stages of specific conditions. Currently, clinical studies are mainly based on subjective, visual assessment, with limited repeatability and inter-observer agreement. To address these problems, we propose a fully automated framework for image-level tortuosity estimation, consisting of a hybrid segmentation method and a highly adaptable, definition-free tortuosity estimation algorithm. The former combines an appearance model, based on a Scale and Curvature-Invariant Ridge Detector (SCIRD), with a context model, including multi-range learned context filters. The latter is based on a novel tortuosity estimation paradigm in which discriminative, multi-scale features can be automatically learned for specific anatomical objects and diseases. Experimental results on 140 in vivo confocal microscopy images of corneal nerve fibres from healthy and unhealthy subjects demonstrate the excellent performance of our method compared to state-of-the-art approaches and ground truth annotations from 3 expert observers.

PURPOSE: To study the clinical features of endogenous endophthalmitis (EE) in sample patient populations from the USA and South Korea over an 8-year period. METHODS: We reviewed data from 128 eyes of 60 American and 48 Korean patients diagnosed with EE and compared their clinical characteristics. RESULTS: Fungemia and liver abscess were the most common extraocular infection sources among American (26.7%) and Korean patients (33.3%), respectively. Klebsiella pneumoniae and Candida species were the most common pathogens of EE in the Korean and the American patients, respectively. Endophthalmitis caused by fungi had a better visual prognosis than that caused by bacteria (p = 0.001). Vitrectomy was beneficial for eyes with EE due to virulent bacteria presenting with worse than counting finger vision. CONCLUSIONS: The predisposing conditions and responsible organisms for EE vary in different regions of the world. The visual prognosis was strongly influenced by the underlying pathogen.

AIMS: To describe and compare clinical features, complications and outcomes in patients with granulomatosis with polyangiitis (GPA)-associated scleritis with those seen in idiopathic and other autoimmune-associated scleritis, and to further describe the features that may serve as an indicator of life-threatening systemic disease. METHODS: We retrospectively reviewed electronic health records of all patients with scleritis seen at two tertiary care centres. Of 500 patients, 14 had GPA-associated scleritis and were included in this analysis. Measures included were age, gender, laterality, visual acuity and underlying systemic or ocular diseases. Clinical features (location, pain, inflammation) and ocular complications of these patients (decrease of vision, concomitant anterior uveitis and ocular hypertension) were studied and correlated. RESULTS: Fourteen of 500 patients with scleritis were GPA associated. Most of the patients with GPA-associated scleritis presented with sudden onset, bilateral, diffuse anterior scleral inflammation, with moderate-or-severe pain. Vision loss was not significantly different, and pain was more severe in these patients than in those with idiopathic scleritis. When compared with patients with other underlying autoimmune diseases, there were no significant differences found in epidemiological or clinical signs. Necrotising scleritis and corneal involvement were more commonly observed in GPA than in idiopathic scleritis and other autoimmune diseases and are often the presenting feature of the disease. CONCLUSIONS: The presence of necrotising changes or corneal involvement in the setting of scleral inflammation is highly suggestive of an underlying systemic vasculitis, of which GPA is the most common. These features should alert the doctor/optometrist and prompt a thorough diagnostic approach and an aggressive treatment given that it could reveal a life-threatening disease.

PURPOSE: Although it has been known that patients' perspectives on their disease can significantly affect their level of functional disability as well as disease outcome, limited data are available on patients' perceptions of their dry eye disease (DED). The aim of this questionnaire-based study was to evaluate patients' perspectives on their DED. METHODS: This cross-sectional study included 91 patients with DED. In addition to clinical evaluation, all patients completed a questionnaire to evaluate their perspectives on their DED. This included their satisfaction with understanding DED, their opinion on the easiness of following doctors' advice, their opinion on the effectiveness of the treatment, their satisfaction with the eye care, and their general outlook on DED. RESULTS: This study included 75 (82%) women and 16 men (18%) with a mean age of 57 ± 14 years who had been treated for DED for 5.2 ± 5.4 years. 93% of the patients were satisfied with their understanding of DED, and 76% found it easy to follow their doctors' advice for DED management. Furthermore, 95% thought that the DED treatment had been helpful and 95% were satisfied with their eye care for DED. Forty-eight percent expressed optimism regarding the long-term prospects of their DED. CONCLUSIONS: Although the majority of DED patients have positive perspectives on their disease, close to half report a lack of optimism regarding the long-term outlook for their condition.

PURPOSE: The Argus II Retinal Prosthesis System (Second Sight Medical Products, Inc, Sylmar, CA) was developed to restore some vision to patients blind as a result of retinitis pigmentosa (RP) or outer retinal degeneration. A clinical trial was initiated in 2006 to study the long-term safety and efficacy of the Argus II System in patients with bare or no light perception resulting from end-stage RP. DESIGN: Prospective, multicenter, single-arm clinical trial. Within-patient controls included the nonimplanted fellow eye and patients' native residual vision compared with their vision with the Argus II. PARTICIPANTS: Thirty participants in 10 centers in the United States and Europe. METHODS: The worse-seeing eye of blind patients was implanted with the Argus II. Patients wore glasses mounted with a small camera and a video processor that converted images into stimulation patterns sent to the electrode array on the retina. MAIN OUTCOME MEASURES: The primary outcome measures were safety (the number, seriousness, and relatedness of adverse events) and visual function, as measured by 3 computer-based, objective tests. Secondary measures included functional vision performance on objectively scored real-world tasks. RESULTS: Twenty-four of 30 patients remained implanted with functioning Argus II Systems at 5 years after implantation. Only 1 additional serious adverse event was experienced after the 3-year time point. Patients performed significantly better with the Argus II on than off on all visual function tests and functional vision tasks. CONCLUSIONS: The 5-year results of the Argus II trial support the long-term safety profile and benefit of the Argus II System for patients blind as a result of RP. The Argus II is the first and only retinal implant to have market approval in the European Economic Area, the United States, and Canada.

IMPORTANCE: Internet-based search engine and social media data may provide a novel complementary source for better understanding the epidemiologic factors of infectious eye diseases, which could better inform eye health care and disease prevention. OBJECTIVE: To assess whether data from internet-based social media and search engines are associated with objective clinic-based diagnoses of conjunctivitis. DESIGN, SETTING, AND PARTICIPANTS: Data from encounters of 4143 patients diagnosed with conjunctivitis from June 3, 2012, to April 26, 2014, at the University of California San Francisco (UCSF) Medical Center, were analyzed using Spearman rank correlation of each weekly observation to compare demographics and seasonality of nonallergic conjunctivitis with allergic conjunctivitis. Data for patient encounters with diagnoses for glaucoma and influenza were also obtained for the same period and compared with conjunctivitis. Temporal patterns of Twitter and Google web search data, geolocated to the United States and associated with these clinical diagnoses, were compared with the clinical encounters. The a priori hypothesis was that weekly internet-based searches and social media posts about conjunctivitis may reflect the true weekly clinical occurrence of conjunctivitis. MAIN OUTCOMES AND MEASURES: Weekly total clinical diagnoses at UCSF of nonallergic conjunctivitis, allergic conjunctivitis, glaucoma, and influenza were compared using Spearman rank correlation with equivalent weekly data on Tweets related to disease or disease-related keyword searches obtained from Google Trends. RESULTS: Seasonality of clinical diagnoses of nonallergic conjunctivitis among the 4143 patients (2364 females [57.1%] and 1776 males [42.9%]) with 5816 conjunctivitis encounters at UCSF correlated strongly with results of Google searches in the United States for the term pink eye (ρ, 0.68 [95% CI, 0.52 to 0.78]; P < .001) and correlated moderately with Twitter results about pink eye (ρ, 0.38 [95% CI, 0.16 to 0.56]; P < .001) and with clinical diagnosis of influenza (ρ, 0.33 [95% CI, 0.12 to 0.49]; P < .001), but did not significantly correlate with seasonality of clinical diagnoses of allergic conjunctivitis diagnosis at UCSF (ρ, 0.21 [95% CI, -0.02 to 0.42]; P = .06) or with results of Google searches in the United States for the term eye allergy (ρ, 0.13 [95% CI, -0.06 to 0.32]; P = .19). Seasonality of clinical diagnoses of allergic conjunctivitis at UCSF correlated strongly with results of Google searches in the United States for the term eye allergy (ρ, 0.44 [95% CI, 0.24 to 0.60]; P < .001) and eye drops (ρ, 0.47 [95% CI, 0.27 to 0.62]; P < .001). CONCLUSIONS AND RELEVANCE: Internet-based search engine and social media data may reflect the occurrence of clinically diagnosed conjunctivitis, suggesting that these data sources can be leveraged to better understand the epidemiologic factors of conjunctivitis.

PURPOSE: To report the ocular manifestations of phospholipase-Cγ2-associated antibody deficiency and immune dysregulation (PLAID). METHODS: Case report and literature review. RESULTS: A 21-year-old woman diagnosed with PLAID was referred for evaluation of repeated episodes of ocular inflammation resulting in bilateral peripheral corneal pannus with episcleritis and corneal scarring accompanied by systemic manifestations including epidermolysis bullosa and interstitial lung disease. Systemic immunosuppression with corticosteroids and interleukin-1 (IL-1) receptor antagonist (anakinra) was supplemented with topical anakinra to avoid systemic side effects, which resulted in partial improvement of the ocular symptoms. Oral prednisone was restarted to treat active lesions during bouts of inflammation. CONCLUSIONS: Ocular PLAID is a bilateral chronic or recurrent inflammatory disease of the ocular surface leading to severe and early cicatricial ocular surface and corneal involvement because of high IL-1 production. Management of PLAID may require both topical and systemic immunomodulatory treatments, potentially including targeted local anti-IL-1 therapy.

The G309 allele of SNPs in the mouse double minute (MDM2) promoter locus is associated with a higher risk of cancer and proliferative vitreoretinopathy (PVR), but whether SNP G309 contributes to the pathogenesis of PVR is to date unknown. The clustered regularly interspaced short palindromic repeats (CRISPR)-associated endonuclease (Cas) 9 from Streptococcus pyogenes (SpCas9) can be harnessed to manipulate a single or multiple nucleotides in mammalian cells. Here we delivered SpCas9 and guide RNAs using dual adeno-associated virus-derived vectors to target the MDM2 genomic locus together with a homologous repair template for creating the mutation of MDM2 T309G in human primary retinal pigment epithelial (hPRPE) cells whose genotype is MDM2 T309T. The next-generation sequencing results indicated that there was 42.51% MDM2 G309 in the edited hPRPE cells using adeno-associated viral CRISPR/Cas9. Our data showed that vitreous induced an increase in MDM2 and subsequent attenuation of p53 expression in MDM2 T309G hPRPE cells. Furthermore, our experimental results demonstrated that MDM2 T309G in hPRPE cells enhanced vitreous-induced cell proliferation and survival, suggesting that this SNP contributes to the pathogenesis of PVR.