According to current projections, the number of Americans with diabetes mellitus will increase from 27.8 million in 2007 to 60.7 million in 2030. With the increasing gap between demand for eye care and supply of ophthalmologists and optometrists, and the non-uniform distribution of eye care providers in US counties, barriers to eye examinations will likely increase. Telemedicine assessment of diabetic retinal disease through remote retinal imaging and diagnosis has the potential to meet these growing demands. To establish evidence for a telemedicine program as an effective modality for diabetic retinopathy (DR) assessment, the interpretation of teleretinal images should compare favorably with Early Treatment Diabetic Retinopathy Study film or digital photographs. We review the current evidence on the critical features and characteristics of ocular telehealth programs for DR in the following categories: image gradability, mydriasis, sensitivity and specificity, cost-effectiveness, long-term effectiveness, patient comfort and satisfaction, and improvement of patient related outcomes.

Acute acquired comitant esotropia (AACE) is characterized by a sudden-onset eye misalignment with an equal angle of deviation in all fields of gaze. This form of esotropia is distinct from common forms of childhood esotropia, such as infantile esotropia and accommodative esotropia, in the rapid tempo and typically later timing of onset; further, AACE is distinct from restrictive or paretic strabismus, which usually results in an incomitant angle of deviation that varies with the direction of gaze. The underlying etiologies for AACE are broad but, in some cases, it may be associated with significant neurologic disease. Therefore, the purpose of this article is to examine and summarize the current literature on AACE to provide a framework for the evaluation and management of this form of acquired strabismus.

Retinitis pigmentosa is a genetically heterogeneous disorder with an estimated prevalence of one in 4,000 that is classically characterized by the progressive constriction of peripheral vision and a later deterioration of visual acuity. Central vision can be compromised earlier in disease, however, in the approximately 25% of patients that have cystoid macular edema. This poorly understood problem can thus significantly impair patient quality of life, particularly as available treatments have limited efficacy. We will review clinical features of retinitis pigmentosa-associated cystoid macular edema, potential causative mechanisms, and finally, evidence supporting currently employed therapies with emphasis upon which management strategies require further evidence-based evaluation.

Endothelial keratoplasty (EK) has replaced penetrating keratoplasty (PKP) as the preferred surgical therapy for corneal endothelial dysfunction. However, recent nationwide corneal graft registry data showed few advantages to EK relative to PKP with respect to graft survival and visual outcomes. This article compares the published outcomes and complications of EK to those of PKP. EK demonstrates superior spectacle corrected visual outcomes, fast recovery, less graft rejection, and higher patient satisfaction, particularly in studies performed by high-volume surgeons/centers. Endothelial cell loss in EK, while higher at early time points, was equivalent or superior at five-years' follow-up and graft survival was equivalent to or superior to PKP in these centers/studies. Continued standardization and simplification of EK procedures may allow surgeons who perform a lower volume of EK to achieve results that mirror those of high-volume centers/surgeons and close the potential gap in outcomes demonstrated in the registry data.

PURPOSE: To evaluate the feasibility of Descemet stripping endothelial keratoplasty using grafts preloaded by an eye bank in a commercially available insertion device. METHODS: In this retrospective case series, a series of 35 eyes in 34 consecutive patients who underwent Descemet stripping endothelial keratoplasty for Fuchs endothelial dystrophy or previously failed full-thickness grafts at a single tertiary care center from March 2013 to March 2014 was included. The donor tissue had undergone pre-lamellar dissection, trephination, and loading into EndoGlide Ultrathin inserters at the Lions Eye Institute for Transplant and Research (Tampa, FL) and was shipped overnight in Optisol GS to the surgeon (K.C.). Surgery was performed within 24 hours from tissue preparation and loading by the eye bank. Donor and recipient characteristics, endothelial cell density (ECD), best-corrected visual acuity, and central corneal thickness were recorded. The main outcome measures were intraoperative and postoperative complications and ECD loss at 3, 6, and 12 months. RESULTS: One primary graft failure (2.8%), 2 rebubblings (5.7%), and 1 graft rejection (2.8%) occurred. Mean preoperative donor ECD was 2821 ± 199 cells/mm. Six months postoperatively, the mean endothelial cell loss was 25.3% ± 17.2% (n = 32), which remained stable at 1 year (31.5% ± 17.9%, n = 32). Mean best-corrected visual acuity improved from 20/100 preoperatively to 20/25 at a mean follow-up of 1 year (n = 32). Mean central corneal thickness was reduced from 711 ± 110 μm to 638 ± 66 μm at the last follow-up visit. CONCLUSIONS: Donor graft tissue preloaded by an eye bank can be used successfully for endothelial keratoplasty. Preloading reduces intraoperative tissue manipulation.

Diabetic retinopathy (DR) is the most frequent microvascular complication from diabetes and requires annual screening and at least annual follow-up. A systemic approach to optimize blood glucose and blood pressure may halt progression to severe stages of DR and obviate the need for ocular treatment. Although there is evidence of benefit from fenofibrate or intravitreous antiVEGF treatment for eyes with nonproliferative DR (NPDR), these therapies are not standard care for NPDR at this time. Some patients with severe NPDR, especially those with type 2 diabetes, benefit from early panretinal photocoagulation (PRP). Once DR progresses to proliferative DR (PDR), treatment is often necessary to prevent visual loss. PRP remains mainstay treatment for PDR with high-risk characteristics. However, intravitreous antiVEGF injections appear to be a safe and effective treatment alternative for PDR through at least two years. Vitreoretinal surgery is indicated for PDR cases with non-clearing vitreous hemorrhage and/or tractional retinal detachment.

Pattern recognition receptors (PRRs) are critical to the early detection and innate immune responses to pathogens. In particular, the toll-like receptor (TLR) system and its associated adaptor proteins have essential roles in early host responses to infection. Epidemic keratoconjunctivitis, caused by the human adenovirus, is a severe ocular surface infection associated with corneal inflammation (stromal keratitis). We previously showed that adenovirus capsid was a key molecular pattern in adenovirus keratitis, with viral DNA having a lesser role. We have now investigated the role of the adaptor molecule MyD88 in a mouse model of adenovirus keratitis in which there is no viral replication. In MyD88(-/-) mice infected with human adenovirus type 37, clinical keratitis was markedly reduced, along with infiltration of CD45(+) cells, and expression of inflammatory cytokines. Reduction of inflammatory cytokines was also observed in infected primary human corneal fibroblasts pretreated with a MyD88 inhibitory peptide. Keratitis similar to wild type mice was observed in TLR2, TLR9 and IL-1R knockout mice, but was reduced in TLR2/9 double knockout mice, consistent with synergy of TLR2 and TLR9 in the response to adenovirus infection. MyD88 co-immunoprecipitated with Src kinase in mice corneas and in human corneal fibroblasts infected with adenovirus, and MyD88 inhibitory peptide reduced Src phosphorylation, linking MyD88 activation to inflammatory gene expression through a signaling cascade previously shown to be directed by Src. Our findings reveal a critical role for the PRRs TLR2 and 9, and their adaptor protein MyD88, in corneal inflammation upon adenovirus infection.

Retinopathy of prematurity (ROP) is a neurovascular disease that affects prematurely born infants and is known to have significant long term effects on vision. We conducted the studies described herein not only to learn more about vision but also about the pathogenesis of ROP. The coincidence of ROP onset and rapid developmental elongation of the rod photoreceptor outer segments motivated us to consider the role of the rods in this disease. We used noninvasive electroretinographic (ERG), psychophysical, and retinal imaging procedures to study the function and structure of the neurosensory retina. Rod photoreceptor and post-receptor responses are significantly altered years after the preterm days during which ROP is an active disease. The alterations include persistent rod dysfunction, and evidence of compensatory remodeling of the post-receptor retina is found in ERG responses to full-field stimuli and in psychophysical thresholds that probe small retinal regions. In the central retina, both Mild and Severe ROP delay maturation of parafoveal scotopic thresholds and are associated with attenuation of cone mediated multifocal ERG responses, significant thickening of post-receptor retinal laminae, and dysmorphic cone photoreceptors. These results have implications for vision and control of eye growth and refractive development and suggest future research directions. These results also lead to a proposal for noninvasive management using light that may add to the currently invasive therapeutic armamentarium against ROP.

PURPOSE: To report the long-term visual outcomes and complications after Boston keratoprosthesis type II implantation in the largest single-center case series with the longest average follow-up. DESIGN: Retrospective review of consecutive clinical case series. PARTICIPANTS: Between January 1992 and April 2015 at the Massachusetts Eye and Ear Infirmary, 48 eyes of 44 patients had keratoprosthesis type II implanted by 2 surgeons (C.H.D. and J.C.). METHODS: For each eye, data were collected and analyzed on the preoperative characteristics, intraoperative procedures, and postoperative course. MAIN OUTCOME MEASURES: Visual acuity outcomes, postoperative complications, and device retention. RESULTS: The most common indications for surgery were Stevens-Johnson syndrome in 41.7% (20 of 48 eyes) and mucous membrane pemphigoid in 41.7% (20 of 48 eyes). Mean follow-up duration was 70.2 months (standard deviation, 61.8 months; median, 52 months; range, 6 months to 19.8 years). Almost all patients (95.8%, 46 of 48 eyes) had a preoperative visual acuity of 20/200 or worse. Postoperative visual acuity improved to 20/200 or better in 37.5% (18 of 48 eyes) and to 20/100 or better in 33.3% (16 of 48 eyes) at the last follow-up visit. The most common postoperative complication was retroprosthetic membrane formation in over half (60.4%, 29 of 48 eyes). The most pressing postoperative complication was glaucoma onset or progression in about a third. Preexisting glaucoma was present in 72.9% (35 of 48 eyes). Glaucoma progressed in 27.1% (13 of 48 eyes) and was newly diagnosed in 8.3% (4 of 48 eyes) after surgery. Other postoperative complications were tarsorrhaphy revision in 52.1% (25 of 48 eyes), retinal detachment in 18.8% (9 of 48 eyes), infectious endophthalmitis in 6.3% (3 of 48 eyes), and choroidal detachment or hemorrhage in 8.3% (4 of 48 eyes). Half of eyes retained their initial keratoprosthesis at the last follow-up (50.0%, 24 of 48 eyes). CONCLUSIONS: The Boston keratoprosthesis type II is a viable option to salvage vision in patients with poor prognosis for other corneal procedures. Retroprosthetic membranes, keratoprosthesis retention, and glaucoma are major challenges in the postoperative period; however, the keratoprosthesis can still provide improved vision in a select group of patients.

PURPOSE: To compare postoperative ocular surface integrity and innervation between small incision lenticule extraction (SMILE) and femtosecond laser-assisted laser in situ keratomileusis (FS-LASIK). METHODS: The Cochrane Central Register of Controlled Trials, PubMED, and EMBASE were searched for prospective comparative studies. Trials meeting the selection criteria were quality appraised, and the data were extracted by 2 independent authors. The weighted mean differences (WMDs) and 95% confidence intervals (CIs) were used to compare dry eye examinations and corneal subbasal nerve density (SMILE-FS-LASIK). RESULTS: The study covered 5 trials. No significant difference was found in the Schirmer test score between both groups (WMD = -1.91 and 0.27; 95% CI, -5.02 to 1.20 and -0.99 to 1.54; P = 0.23 and 0.67 at 1- and 6-month follow-ups, respectively). Tear breakup time in the SMILE group significantly exceeded that in the FS-LASIK group (WMD = 0.65 and 1.14; 95% CI, 0.20-1.10 and 0.18-2.10; P = 0.004 and 0.02, at 1- and 6-month follow-ups, respectively). Ocular surface disease index scores were significantly better in the SMILE group 6 months postoperatively (WMD = -10.12, 95% CI, -16.07 to -4.18, P = 0.0008). No significant difference was found in tear osmolarity between both groups (WMD = -5.19 and -6.37; 95% CI, -17.15 to 6.76 and -22.74 to 10.00; P = 0.39 and 0.45 at 1- and 6-month follow-ups, respectively). Higher corneal sensitivity was observed in the SMILE group 1 and 6 months postoperatively (WMD = 11.35 and 3.49; 95% CI, 7.29-15.40 and 1.76-5.21; P < 0.00001 and <0.0001, at 1- and 6-month follow-ups, respectively). Corneal subbasal nerve density was also significantly higher in SMILE-treated eyes than it was in FS-LASIK-treated eyes 1 month postoperatively (WMD = 4.72, 95% CI, 1.10-8.34, P = 0.01). CONCLUSIONS: According to this meta-analysis, the SMILE procedure has fewer negative impacts on the ocular surface and corneal innervation than does FS-LASIK. Furthermore, SMILE shows superiority over FS-LASIK by a exhibiting a lower risk of postoperative dry eye.

PURPOSE: Patching for double vision is a common palliative treatment for head-trauma patients with acquired strabismus when prisms are not feasible. METHODS: We review literature on spatial neglect and discuss possible effects of monocular occlusion on spatial attention. RESULTS: Patching the left eye has been shown to worsen spatial judgments in some brain-injured patients with left neglect by inhibiting the right superior colliculus further impairing contralateral leftward orienting (the Sprague Effect). CONCLUSIONS: Because more peripheral parts of the visual field increasingly project to the contralateral superior colliculus with the temporal crescent being entirely contralateral, avoiding patching of the temporal crescent was advised, and in most cases can be achieved by taping off the spectacle lens and avoiding an elastic eye patch.

PURPOSE: Corneal neuropathy is a recently described disease process that is not well understood and is likely underdiagnosed as a result. This is the first reported case of an acquired corneal neuropathy associated with malposition of an Ex-PRESS shunt. METHODS: A single case report. RESULTS: We report the case of a 50-year-old man with a history of multiple procedures for glaucoma who subsequently developed photoallodynia and corneal neuropathy in association with malposition of an Ex-PRESS shunt in the peripheral cornea. Laser confocal microscopy (HRT3/RCM) of the cornea showed the presence of neuromas, decreased nerve density, and a significant increase of dendritiform immune cells consistent with our diagnosis. Initial treatment with steroid pulse therapy did not result in decreased inflammation or symptomatic improvement leading to surgical explantation of the shunt. One month after surgery, there was noticeable improvement in the patient's pain and photoallodynia (approximately 40%) as well as the abnormalities seen on confocal microscopy. CONCLUSIONS: We hypothesize that poor Ex-PRESS shunt positioning can act as a nidus for corneal inflammation, resulting in corneal neuropathy and lowering of the nociception threshold.

PURPOSE: The development of a suitable storage method for retinal pigment epithelium (RPE) is necessary in the establishment of future RPE replacement therapy, and storage temperature has proven to be pivotal for cell survival. ARPE-19, a widely used model for RPE, has been shown to yield the greatest number of viable cells when stored at 16°C compared to other storage temperatures. In this study, we analyze the gene expression profile of cultured ARPE-19 cells after seven days of storage at different temperatures in an effort to predict the gene-level consequences of storage of RPE transplants. MATERIALS AND METHODS: ARPE-19 cells were cultured until confluence and then stored in minimum essential medium at 4°C, 16°C, and 37°C for seven days. The total RNA was isolated and the gene expression profile was determined using DNA microarrays. The Results were validated using qPCR. RESULTS: Principal component and hierarchical clustering analyses show that the gene expression profiles of cell cultures stored at different temperatures cluster into separate groups. Cultures stored at 4°C cluster closest to the control cultures that were not stored and display the least change in gene expression after storage (157 differentially expressed genes). Cultures stored at 16°C and 37°C display a much larger change in differential gene expression (1787 and 1357 differentially expressed genes, respectively). At 16°C, the expression of several genes with proposed tumor suppressor functions was markedly increased. Changes in regulation of several known signaling pathways and of oxidative stress markers were discovered at both 16°C and 37°C, and activation of the angiogenesis marker vascular endothelial growth factor (VEGF) was discovered at 37°C. There was no evidence of the activation of inflammatory processes in stored cell cultures. CONCLUSION: ARPE-19 cultures stored at 16°C show the greatest propensity to modulate their gene expression profile in a manner that supports cell survival during storage.

Conjunctival goblet cells play a major role in maintaining the mucus layer of the tear film under physiological conditions as well as in inflammatory diseases like dry eye and allergic conjunctivitis. Resolution of inflammation is mediated by proresolution agonists such as lipoxin A4 (LXA4) that can also function under physiological conditions. The purpose of this study was to determine the actions of LXA4 on cultured rat conjunctival goblet cell mucin secretion, intracellular [Ca(2+)] ([Ca(2+)]i), and identify signaling pathways activated by LXA4. ALX/FPR2 (formyl peptide receptor2) was localized to goblet cells in rat conjunctiva and in cultured goblet cells. LXA4 significantly increased mucin secretion, [Ca(2+)]i, and extracellular regulated kinase 1/2 (ERK 1/2) activation. These functions were inhibited by ALX/FPR2 inhibitors. Stable analogs of LXA4 increased [Ca(2+)]i to the same extent as LXA4. Sequential addition of either LXA4 or resolvin D1 followed by the second compound decreased [Ca(2+)]i of the second compound compared with its initial response. LXA4 activated phospholipases C, D, and A2 and downstream molecules protein kinase C, ERK 1/2, and Ca(2+)/calmodulin-dependent kinase to increase mucin secretion and [Ca(2+)]i. We conclude that conjunctival goblet cells respond to LXA4 to maintain the homeostasis of the ocular surface and could be a novel treatment for dry eye diseases.

A 55-year-old woman had a right orbital cyst detected incidentally on radiographic imaging. The patient's symptoms were mild and included intermittent pain and vertical diplopia; the patient was not aware of any visual decline. There was a palpable mass beneath the superior orbital rim. Radiographic imaging revealed a well-demarcated cystic lesion in the right superior orbit between the levator palpebrae superioris and superior rectus muscles. The mass was completely excised via a transconjunctival approach. Histopathologic evaluation disclosed a conjunctival cyst lined by nonkeratinized squamous epithelium with scattered, rare goblet cells. This case combined with 5 other similar reported cases suggests that an intermuscular cyst located in the superior rectus-levator complex is most likely of congenital embryonic conjunctival origin.