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Vision loss and blindness are among the top ten disabilities in the United States, yet access and utilization of eye care remains low. Vision Detroit aimed to address eye-care disparities via community-based screenings. By investigating burden of eye disease and barriers to eye-care utilization in an underserved urban community, we may direct efforts to improve access.Twenty-three screenings were conducted from March 2015-November 2017. Patient information gathered at screenings were demographics, medical and social history, eye exam/referral history, insurance status, primary care physician (PCP) status, and patient-perceived eye-care barriers.Three-hundred-eighty patients were screened, 42% African American and 51% Hispanic. Average age was 53 ± 16.4 years, 70% reported vision problems, 50% reported over two years of vision problems, and average habitual visual acuity in best-seeing eye was 20/37. Eye-care underutilization was reported in 61% of type-2 diabetics. Older age and PCP recommendations/referrals were associated with increased utilization in all patients. Insurance was the most common barrier (53%); of the 55% insured, 31% reported financial barriers. Employed patients were more likely than unemployed to report a time barrier (odds ratio = 1.76, 95% confidence interval 1.03-3.01). Those with high school or less education reported "unaware of need", "unsure where to go", "transportation", and "insurance" as barriers more often.Visual burden was pervasive, yet access was suboptimal. Financial, logistical, and awareness barriers were common. PCP referral and older age were associated with increased utilization. Those less educated reported more barriers, highlighting the need to address fiscal concerns and eye-health education.

Anion channels in the retinal pigment epithelium (RPE) play an essential role in the transport of Cl− between the outer retina and the choroidal blood to regulate the ionic composition and volume of the subretinal fluid that surrounds the photoreceptor outer segments. Recently, we reported that the anion conductance of the mouse RPE basolateral membrane is highly selective for the biologically active anion thiocyanate (SCN−), a property that does not correspond with any of the Cl− channels that have been found to be expressed in the RPE to date. The purpose of this study was to determine the extent to which SLC26A7, a SCN− permeable-anion exchanger/channel that was reported to be expressed in human RPE, contributes to the RPE basolateral anion conductance. We show by quantitative RT-PCR that Slc26a7 is highly expressed in mouse RPE compared with other members of the Slc26 gene family and Cl− channel genes known to be expressed in the RPE. By applying immunofluorescence microscopy to mouse retinal sections and isolated cells, we localized SLC26A7 to the RPE basolateral membrane. Finally, we performed whole cell and excised patch recordings from RPE cells acutely isolated from Slc26a7 knockout mice to show that the SCN− conductance and permeability of its basolateral membrane are dramatically smaller relative to wild-type mouse RPE cells. These findings establish SLC26A7 as the SCN−-selective conductance of the RPE basolateral membrane and provide new insight into the physiology of an anion channel that may participate in anion transport and pH regulation by the RPE.

Purpose: To investigate the frequency of conjunctival erosions in a series of patients who underwent Ahmed valve implantation in a tertiary referral center and to study risk factors associated with the conjunctival erosions. Methods: This is a single-center, retrospective case-control study of all patients who underwent Ahmed valve implantation between October 2006 and July 2016 at the Kresge Eye Institute in Detroit, Michigan. The series consisted of 306 eyes (277 patients) that underwent Ahmed valve implantation. The rate of conjunctival erosions was determined. Univariate, bivariate, and Cox-proportional hazard analyses were performed to identify factors associated with conjunctival erosions. Results: During the study period, 23 erosions occurred in 306 eyes (7.52%). Aphakia was significantly more common in eyes with erosions (P < 0.05). Aphakia (P = 0.02), uveitic glaucoma (P = 0.03), and longer post-operative use of topical steroids (P < 0.04) significantly increased the risk of erosions based on the Cox model. There were similar rates of erosions with each type of patch graft. No conjunctival erosion was observed after using the modified scleral tunnel method (n = 10). Conclusions: The overall erosion rate was 7.52% in our series. Uveitic glaucoma, aphakia, and longer post-operative use of topical steroids were significantly associated with conjunctival erosions.

The daily shedding and renewal of photoreceptor outer segments (OS) is critical for maintaining vision. This process relies on the efficient uptake, degradation, and sorting of shed OS material by the retinal pigment epithelium (RPE). Poor OS degradation has been linked to retinal degenerations such as Stargardt disease and may contribute to macular degeneration. While primary human fetal RPE cultures have emerged as a valuable model of in vivo human RPE function, surprisingly few studies have utilized the model for tracking the degradation and fate of OS components in the RPE. Here, we establish an improved platform for studying this topic by modifying existing protocols and creating new methods. Our human fetal culture model facilitates studies of RPE secretion in response to OS ingestion, preserves RPE differentiation and polarization during live-cell imaging of OS phagocytosis, and minimizes costs. We optimize Mer tyrosine kinase-dependent OS phagocytosis assays specifically in human fetal cultures and provide a simple and accurate method for measuring total OS consumption by the RPE. Finally, we utilize chemical transfection, dextran labeling, and immunocytochemistry to evaluate key players in OS degradation, including lysosomes and autophagy proteins. To facilitate quantification of autophagy vesicles, we develop customized image analysis macros in the Fiji/ImageJ software environment. These protocols will facilitate a broad range of studies in human fetal RPE cultures aimed at determining the ultimate fate of OS components after ingestion, a critical step in understanding the pathogenesis of numerous retinal diseases.

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.

Human, monkey, and bovine retinal pigment epithelial (RPE) cells exhibit an M-type K+ current, which in many other cell types is mediated by channels composed of KCNQ α-subunits and KCNE auxiliary subunits. Recently, we demonstrated the expression of KCNQ1, KCNQ4, and KCNQ5 in the monkey RPE. Here, we investigated the expression of KCNQ and KCNE subunits in native bovine RPE. RT-PCR analysis revealed the expression of KCNQ1, KCNQ4, and KCNQ5 transcripts in the RPE, but, in Western blot analysis of RPE plasma membranes, only KCNQ5 was detected. Among the five members of the KCNE gene family, transcripts for KCNE1, KCNE2, KCNE3, and KCNE4 were detected in bovine RPE, but only KCNE1 and KCNE2 proteins were detected. Immunohistochemistry of frozen bovine retinal sections revealed KCNE1 expression near the apical and basal membranes of the RPE, in cone outer segments, in the outer nuclear layer, and throughout the inner retina. The localization of KCNE1 in the RPE basal membrane, where KCNQ5 was previously found to be present, suggests that this β-subunit may contribute to M-type K(+) channels in this membrane.

Reactive oxygen metabolites (ROMs) may contribute to several eye diseases, such as age-related macular degeneration, although the underlying mechanisms are unclear. The present study shows that human photoreceptor outer segments (POS) prime human retinal pigment epithelial (RPE) cells for massive ROM release in response to lipopolysaccharide (LPS) and interferon-γ. However, no ROM priming of human RPE cells is observed for bovine POS. ROM production appears to be linked with underlying metabolic oscillations involving the hexose monophosphate shunt.

Retinal pigment epithelial (RPE) cells mediate the recognition and clearance of effete photoreceptor outer segments (POS), a process central to the maintenance of normal vision. Given the emerging importance of Toll-like receptors (TLRs) in transmembrane signaling in response to invading pathogens as well as endogenous substances, we hypothesized that TLRs are associated with RPE cell management of POS. TLR4 clusters on human RPE cells in response to human, but not bovine, POS. However, TLR4 clustering could be inhibited by saturating concentrations of an inhibitory anti-TLR4 mAb. Furthermore, human POS binding to human RPE cells elicited transmembrane metabolic and calcium signals within RPE cells, which could be blocked by saturating doses of an inhibitory anti-TLR4 mAb. However, the heterologous combination of bovine POS and human RPE did not trigger these signals. The pattern recognition receptor CD36 collected at the POS–RPE cell interface for both homologous and heterologous samples, but human TLR4 only collected at the human POS–human RPE cell interface. Kinetic experiments of human POS binding to human RPE cells revealed that CD36 arrives at the POS–RPE interface followed by TLR4 accumulation within 2 min. Metabolic and calcium signals immediately follow. Similarly, the production of reactive oxygen metabolites (ROMs) was observed for the homologous human system, but not the heterologous bovine POS–human RPE cell system. As (a) the bovine POS/human RPE combination did not elicit TLR4 accumulation, RPE signaling, or ROM release, (b) TLR4 arrives at the POS–RPE cell interface just before signaling, (c) TLR4 blockade with an inhibitory anti-TLR4 mAb inhibited TLR4 clustering, signaling, and ROM release in the human POS–human RPE system, and (d) TLR4 demonstrates similar clustering and signaling responses to POS in confluent RPE monolayers, we suggest that TLR4 of RPE cells participates in transmembrane signaling events that contribute to the management of human POS.

Purpose. To determine the expression and functional activity of proton-coupled oligopeptide transporters (POT) in retinal pigment epithelial (RPE) cells.

To evaluate the long-term effectiveness of glaucoma management in patients undergoing primary glaucoma triple procedure (PGTP) with and without adjunctive subconjunctival mitomycin-C (MMC).Case-controlled study.Of the 203 eyes of 203 primary open-angle glaucoma (POAG) patients who had undergone PGTP and in whom reliable Humphrey visual fields had been obtained both before and after surgery at 13.5 +/- 8.9 and 27.9 +/- 8.9 months, 124 of the 144 eyes that received MMC during surgery were matched to the other 59 eyes that did not with respect to cup-to-disc ratio and risk factors for filtration failure in addition to other variables.Both preoperative and postoperative intraocular pressure (IOP), Humphrey visual fields and their global indices, number of glaucoma medications, and best-corrected visual acuity (BCVA).There were no significant differences in demographics between the two groups (P0.05 for each). Whereas both the control and the MMC groups attained significant decreases of mean IOP (18.5 +/- 5.7 mmHg-;15.6 +/- 4.6 mmHg, P = 0.0014; 19.3 +/- 7.0 mmHg-13.7 +/- 4.9 mmHg, P = 0.0001) and mean number of medications (2.1 +/- 1.3-1.3 +/- 1.3, P = 0.0001; 2.3 +/- 1.2-1.0 +/- 1.3, P = 0.0001) at 36 months after surgery, the MMC group had significantly lower mean IOP than the control group at all postoperative visits (P0.05 for each). The MMC group also tended to have less medical dependency after surgery than the control group. There was no significant difference in postoperative BCVA between the two groups. Patients in both groups had mean visual acuity of 20/30 or better. There was a significant worsening of corrected pattern standard deviation (CPSD) in the control group (3.97 +/- 3.18-5.17 +/- 3.36, P = 0.001) compared with no significant change in the MMC group (5.07 +/- 4.11-5.23 +/- 3.36, P = 0.93). The mean deviation did not change significantly in either group.The long-term glaucoma management in POAG patients with cataract undergoing PGTP indicates a successful outcome in final IOP, medical dependency, and BCVA. Furthermore, the MMC group had better IOP control and stable visual fields (CPSD), whereas the control group had a significant worsening of CPSD.

Human, monkey, and bovine retinal pigment epithelial (RPE) cells exhibit an M-type K+ current, which in many other cell types is mediated by channels composed of KCNQ α-subunits and KCNE auxiliary subunits. Recently, we demonstrated the expression of KCNQ1, KCNQ4, and KCNQ5 in the monkey RPE. Here, we investigated the expression of KCNQ and KCNE subunits in native bovine RPE. RT-PCR analysis revealed the expression of KCNQ1, KCNQ4, and KCNQ5 transcripts in the RPE, but, in Western blot analysis of RPE plasma membranes, only KCNQ5 was detected. Among the five members of the KCNE gene family, transcripts for KCNE1, KCNE2, KCNE3, and KCNE4 were detected in bovine RPE, but only KCNE1 and KCNE2 proteins were detected. Immunohistochemistry of frozen bovine retinal sections revealed KCNE1 expression near the apical and basal membranes of the RPE, in cone outer segments, in the outer nuclear layer, and throughout the inner retina. The localization of KCNE1 in the RPE basal membrane, where KCNQ5 was previously found to be present, suggests that this β-subunit may contribute to M-type K(+) channels in this membrane.

The authors compared the efficacy of apraclonidine 1% versus pilocarpine 4% prophylaxis of post-argon laser trabeculoplasty (ALT) intraocular pressure (IOP) spike.Prospective randomized clinical trial.Two hundred twenty-eight eyes of 228 patients with primary open-angle glaucoma undergoing ALT were studied.Patients were given 1 drop of either apraclonidine 1% (n = 114) or pilocarpine 4% (n = 114) 15 minutes before ALT.Peri-ALT IOPs and incidences of post-ALT IOP spikes at 5 minutes, 1 hour, and 24 hours were compared between the two groups.The two groups were similar in age, race, and medical dependency. Post-ALT mean IOPs at 5 minutes, 1 hour, and 24 hours were significantly lower than pre-ALT mean IOPs in both apraclonidine (P0.001) and pilocarpine (P0.001) groups. Incidences of IOP spikes greater than 1, 3, and 5 mmHg at 1 hour post-ALT were 21.1%, 14.9%, and 8.8% for the apraclonidine group and 12.3%, 5.3%, and 4.4% for the pilocarpine group (P = 0.076, 0.015, and 0.18 chi-square test). In the apraclonidine prophylaxis group, patients on long-term apraclonidine showed significantly higher incidence of post-ALT IOP spike than the patients without such long-term apraclonidine use (35.7%, 15 of 42 eyes, vs. 12.5%, 9 of 72 eyes; P = 0.003). In addition, peri-ALT pilocarpine prophylaxis tended to be less effective in patients undergoing long-term pilocarpine therapy but without statistical significance (17.4%, 8 of 46 eyes, vs. 9.4%, 6 of 64 eyes; P = 0.17).Peri-ALT pilocarpine 4% was at least as effective as, if not more effective than, apraclonidine 1% in post-ALT IOP spike prophylaxis. Peri-ALT apraclonidine prophylaxis was not effective in patients on long-term apraclonidine, and peri-ALT pilocarpine prophylaxis tended to be less effective in patients undergoing long-term pilocarpine therapy. Pilocarpine 4% can be considered as a first-choice drug for post-ALT IOP spike prophylaxis, especially in patients under treatment with apraclonidine.

Objective To assess the efficacy of latanoprost additive therapy in patients with intraocular pressure (IOP) out of control while taking maximum-tolerated medications and to determine whether pilocarpine therapy has a dose-dependent adverse effect on the efficacy of latanoprost therapy. Design Noncomparative case series. Participants Sixty-one eyes of 61 patients with chronic glaucoma with IOP out of control while receiving maximum-tolerated medications were treated with latanoprost additive therapy on a compassionate basis. Main outcome measures Follow-up was up to 22 months with a mean of 13.9 ± 5.7 months. Kaplan-Meier survival analysis with Mantel-Cox log-rank test was performed to determine the overall success of latanoprost additive therapy and to compare the success rates of high-dose pilocarpine, low-dose pilocarpine, and no pilocarpine therapies. The criterion for success was avoiding glaucoma surgery with IOP decrease of 20% or greater and final IOP less than 22 mmHg. The IOP change and its significance for patients satisfying and failing the criterion for success also were determined to assess the latanoprost additive therapy. In addition, a number of pretreatment variables, including pilocarpine therapy, were analyzed for a significant effect on the efficacy of latanoprost additive therapy using Cox proportional hazards regression analysis. Results Latanoprost additive therapy significantly lowered mean IOP by 3.9 ± 5.5 mmHg at 3 months and by 3.5 ± 5.8 mmHg at 12 months. The cumulative success rate of the latanoprost additive therapy was 70% at 1 month, 42% at 3 months, 40% at 6 months, and 30% at 12 months. Of the variables studied, only increased number of previous incisional glaucoma surgeries and IOP greater than 24 mmHg before latanoprost additive therapy were significant prognostic factors for failure of latanoprost additive therapy. Pilocarpine therapy in any dose had no significant effect. Conclusion This study supports a trial of latanoprost additive therapy before glaucoma surgery in patients with IOP out of control while receiving maximum-tolerated medications irrespective of pilocarpine therapy and the pilocarpine dosage, especially when the number of previous incisional glaucoma surgery is less than three and the IOP is less than 25 mmHg.

To investigate the effect of adjunctive mitomycin C on primary glaucoma triple procedure in patients with primary open-angle glaucoma with and without one or more of the prognostic factors for filtration failure of primary glaucoma triple procedure. Those factors include being of African-American race, having a preoperative intraocular pressure of 20 mm Hg or more on maximum tolerated medications, and being on two or more medications preoperatively.Study patients consisted of 197 consecutive patients with primary open-angle glaucoma who were randomly assigned to receive either no adjunctive mitomycin C (101 eyes of 101 patients) or to receive adjunctive subconjunctival mitomycin C (96 eyes of 96 patients) during the primary glaucoma triple procedure. Kaplan-Meier survival analysis comparisons were made between respective subgroups with and without prognostic indicators for filtration failures using a relatively stringent set of criteria for filtration success of primary glaucoma triple procedure.There was no statistically significant (P = .117) difference in filtration success of primary glaucoma triple procedure between the control and mitomycin C groups. Adjunctive mitomycin C significantly (P.05) improved the filtration outcome of the primary glaucoma triple procedure in the subgroups with each of the three prognostic factors for filtration failure of primary glaucoma triple procedure. On the other hand, in the subgroups without the prognostic factors, adjunctive mitomycin C did not significantly (P.05) change the filtration outcome of the primary glaucoma triple procedure.These findings establish the basis for selective use of mitomycin C in patients with primary open-angle glaucoma undergoing primary glaucoma triple procedure.

The translocation of ions, fluid and macromolecules across epithelia is made possible by the asymmetric distribution of transport proteins, enzymes and receptors in two physically distinct plasma membrane domains that form the apical and basolateral sides of the cell. Each side faces a different extracellular environment. In the back of the vertebrate eye, the retinal pigment epithelium (RPE) apical membrane receives a continuous stream of paracrine signals that are generated by a variety of retinal neurons in the light and dark. These signals help regulate RPE function, and conversely, alterations in RPE function can modify the activity of retinal neurons. At the basolateral surface, there is a continual exchange of nutrients and waste products, along with a flow of hormonal signals from the choroidal blood supply, all of which serve to maintain the health and integrity of the distal retina and in particular, the photoreceptors. This review provides an integrated summary of the apical and basolateral membrane and intracellular signaling mechanisms that mediate the vectorial traffic of ions and fluid across the RPE. These same mechanisms help regulate the chemical milieu within the cell and in the extracellular spaces that surround the cell. They also generate specific components of the electrical signals that are recorded clinically across the intact human eye, the electroretinogram (ERG) and the electrooculogram (EOG). The last part of this review is focused on the light-induced photoreceptor-dependent decrease in subretinal potassium concentration ([K] 0 ) that occurs in the intact eye and serves as a paracrine signal for the RPE. This signal plays a central role in regulating RPE physiology and in mediating retina/RPE interactions, following transitions between light and dark; it is mimicked in vitro by a small (3 m m ) change in [K] 0 on the apical side of the epithelium. The clinical implications are discussed in terms of the transport mechanisms that regulate hydration of the subretinal space and that potentially mediate fluid absorption out of the retina.

Objective: To compare silicone versus acrylic foldable intraocular lens (IOL) implantation in primary glaucoma triple procedure (PGTP). Design: Prospective, randomized. Participants: A total of 79 eyes of 79 primary open-angle glaucoma (POAG) patients in need of combined surgery were randomized to a silicone IOL group (36 eyes) and acrylic IOL group (43 eyes). Intervention: The study eyes underwent PGTP, which consisted of primary trabeculectomy, phacoemulsification, and posterior chamber IOL implantation. Adjunctive mitomycin C (MMC) (0.5 mg/ml for 1 minute) was used selectively only in patients with one or more risk factors for filtration failure of PGTP. Main Outcome Measures: Snellen visual acuity, intraocular pressure (IOP), slitlamp biomicroscopy, and number of glaucoma medications were measured, performed, or determined preoperatively and at regular intervals postoperatively. Results: There were no significant differences in the mean number of postoperative glaucoma medications at 1, 2, 3, 4–6, and 9–12 months and at last follow-up ( P > 0.05); mean change in corrected visual acuity best attained ( P = 0.315) or at last followup ( P = 0.223) between the silicone and acrylic groups. Both groups had significant decreases in mean IOP and mean number of medications postoperatively at all times ( P 25 mmHg and IOP spike > 5 mmHg above preoperative IOP during the first month were significantly higher in the acrylic group ( P = 0.026). The mean postoperative IOP at 1 month in the acrylic group was also significantly higher than the silicone group (14.1 ± 5.0, 11.2 ± 3.9, P = 0.005). Conversely, there were no significant differences in mean postoperative IOP at 2, 3, 4–6, and 9–12 months and at last follow-up between the silicone and acrylic groups ( P > 0.05). Suture removal or release occurred significantly more frequently in the acrylic IOL group during the first month and the first 2 months (48.8% and 60.5%) than the silicone group (25.0% and 36.1%, P = 0.030 and 0.031, respectively). There were no significant differences in postoperative complications or surgical interventions between the two groups ( P > 0.05). Conclusions: During the first year following the PGTP with selective use of MMC, there were no significant differences in the medical dependency or visual outcomes or complications between the silicone and acrylic groups. Both groups attained significant decreases in IOP postoperatively. However, the mean IOP was significantly higher in the acrylic than the silicone group at 1 month postoperatively, and postoperative IOP > 25 mmHg and IOP spike > 5 mmHg above preoperative IOP were significantly greater in the acrylic group. There were significantly more suture releases in the acrylic IOL group than the silicone IOL group in the first 2 months postoperatively.

Purpose: The prerequisite for selective use of adjunctive mitomycin C (MMC) in primary glaucoma triple procedure (PGTP) is a better understanding of the prognostic factors. Therefore, the authors carried out the current study on the outcome of PGTP with and without adjunctive MMC to determine the prognostic factors for filtration failure of PGTP. Methods: The study patients consisted of 174 consecutive primary open-angle glaucoma (POAG) patients undergoing PGTP. They were assigned randomly to either no adjunctive MMC (93 eyes of 93 patients) or adjunctive subconjunctival MMC (81 eyes of 81 patients) during the PGTP. After surgery, the patients were examined at regular intervals for visual acuity, intraocular pressure (IOP) control, medical therapy requirements, and complications. Filtration failure was determined according to two different criteria: (1) a less stringent set of criteria (criterion I) and (2) a more stringent set of criteria (criterion II). Results: There were no statistically significant differences between the groups with and without adjunctive MMC with respect to postoperative IOP, number of medications, and visual acuity outcome during mean follow-up (± standard deviation) of 25.1 ± 5.5 months ( P > 0.05 for each). However, there were prognostic factors for filtration failure in the control group but not in the MMC group. Black race, diabetes mellitus, preoperative IOP greater than or equal to 20 mmHg, and number of preoperative medications greater than two were found to be significant prognostic factors for filtration failure by criterion I. Black race, preoperative IOP greater than or equal to 20 mmHg and number of preoperative medications greater than 1 were significant prognostic factors for filtration failure by criterion II. Conclusion: There was no statistically significant difference in the overall outcome of PGTP between control and MMC groups of nonselected patients with primary openangle glaucoma. Black race, diabetes mellitus (by criterion I only), preoperative IOP greater than or equal to 20 mmHg, and number of preoperative medications greater than 2 (by criterion I) or greater than 1 (by criterion II) were found to be significant independent prognostic factors for filtration failure of PGTP without adjunctive MMC but not with adjunctive MMC. The use of adjunctive subconjunctival MMC in PGTP may have to be selective, primarily in those patients with primary open-angle glaucoma with one or more of the prognostic factors for filtration failure.

Purpose: In 1987, the authors reported the successful eradication of infection in 16 patients with culture-proven acute exogenous bacterial endophthalmitis using intravitreal but no systemic antibiotics. They retrospectively reviewed additional consecutive cases since then to determine if the initial omission of systemic antibiotics remained reasonable. Methods: Twenty patients had culture-proven endophthalmitis. Four patients initially received systemic antibiotics for orbital cellulitis (2 patients), prevention of a possible scleral buckle infection (1 patient), and ascending cholangitis (1 patient). The remaining 16 patients were treated initially with intravitreal antibiotics only. Findings: Three of these additional 16 patients ultimately required systemic antibiotics for orbital cellulitis (1 patient), infectious scleritis (1 patient), and prevention of central nervous system infection with Neisseria meningitidis (1 patient). Only in one patient who had a neglected endophthalmitis and in whom an orbital cellulitis ultimately developed were we unable to clear the intraocular infection. In the overall series of 32 patients, cultures yielded staphylococcal species in 16 eyes, gram-positive bacilli in 3, streptococcal infection in 5, gram-negative cocci in 1, and gram-negative bacilli in 7. Half of the 14 specimens (1 aqueous and 13 vitreal) collected at the time of 16 reinjections in 13 eyes yielded organisms. Half (16/32) of the eyes attained visual acuity of 20/40 or better; 87.5% (28/32) attained visual acuity of 20/400 or better. Conclusions: Therapy with intravitreal antibiotics without systemic antibiotics is reasonable, unless the infection has extended (or is at risk to extend) beyond the globe. Such evidence includes an elevated temperature or leukocyte count, corneal ring abscess, proptosis, loss of extraocular movements, scleral abscesses or infectious scleritis, and, perhaps, the presence of a scleral buckle.

Previous studies identified in retinal pigment epithelial (RPE) cells an M-type K+ current, which in many other cell types is mediated by channels encoded by KCNQ genes. The aim of this study was to assess the expression of KCNQ genes in the monkey RPE and neural retina. Application of the specific KCNQ channel blocker XE991 eliminated the M-type current in freshly isolated monkey RPE cells, indicating that KCNQ subunits contribute to the underlying channels. RT-PCR analysis revealed the expression of KCNQ1, KCNQ4, and KCNQ5 transcripts in the RPE and all five KCNQ transcripts in the neural retina. At the protein level, KCNQ5 was detected in the RPE, whereas both KCNQ4 and KCNQ5 were found in neural retina. In situ hybridization in frozen monkey retinal sections revealed KCNQ5 gene expression in the ganglion cell layer and the inner and outer nuclear layers of the neural retina, but results in the RPE were inconclusive due to the presence of melanin. Immunohistochemistry revealed KCNQ5 in the inner and outer plexiform layers, in cone and rod photoreceptor inner segments, and near the basal membrane of the RPE. The data suggest that KCNQ5 channels contribute to the RPE basal membrane K+ conductance and, thus, likely play an important role in active K+ absorption. The distribution of KCNQ5 in neural retina suggests that these channels may function in the shaping of the photoresponses of cone and rod photoreceptors and the processing of visual information by retinal neurons.

Previously, we demonstrated that the inwardly rectifying K+ (Kir) channel subunit Kir7.1 is highly expressed in bovine and human retinal pigment epithelium (RPE). The purpose of this study was to determine whether any of the 14 other members of the Kir gene family are expressed in native human RPE. Conventional reverse transcription-polymerase chain reaction (RT-PCR) analysis indicated that in addition to Kir7.1, seven other Kir channel subunits (Kir1.1, Kir2.1, Kir2.2, Kir3.1, Kir3.4, Kir4.2 and Kir6.1) are expressed in the RPE, whereas in neural retina, all 14 of the Kir channel subunits examined are expressed. The identities of RT-PCR products in the RPE were confirmed by DNA sequencing. Real-time RT-PCR analysis showed, however, that transcripts of these channels are significantly less abundant than Kir7.1 in the RPE. Western blot analysis of the Kir channel subunits detected in the RPE by RT-PCR revealed the expression of Kir2.1, Kir3.1, Kir3.4, Kir4.2, Kir6.1, and possibly Kir2.2, but not Kir1.1, in both human RPE and neural retina. Our results indicate that human RPE expresses at least five other Kir channel subtypes in addition to Kir7.1, suggesting that multiple members of the Kir channel family may function in this epithelium.

PURPOSE. Mutations in the membrane frizzled-related protein (MFRP) gene cause nanophthalmos in humans, and a splice site mutation causes recessive retinal degeneration in the rd6 mouse. In human and mouse genomes, the MFRP gene lies adjoining to the complement 1q tumor necrosis factor-related protein 5 (CTRP5/C1QTNF5) gene involved in causing retinal degeneration and abnormal lens zonules in human. The purpose of this study was to characterize the spatial and temporal expression of the mouse Mfrp gene, determine tissue and subcellular localization of MFRP protein, and study its interaction with CTRP5. METHODS. Expression of the Mfrp gene in the mouse was studied by quantitative (q)RT-PCR. MFRP protein expression and distribution were studied by Western blot analysis, immunohistochemistry, and immunoelectron microscopy. Interaction with CTRP5 was studied by immunoprecipitation and immunoblot analysis, using mouse eye and human retinal pigmented epithelium (RPE) choroid extracts and by expressing full-length CTRP5 and MFRP in a heterologous system. RESULTS. The Mfrp gene is specifically expressed in RPE and ciliary body (CB), and its expression starts during early stages of embryogenesis. In the albino mouse eye, MFRP is localized to the apical and basal membranes of RPE and ciliary epithelium (CE). In addition, MFRP and CTRP5 were found to colocalize in RPE, CE, and MDCK cells, a general model of polarized epithelia. These proteins interact with each other in ocular tissues and also in a heterologous system. CONCLUSIONS. MFRP is localized to the plasma membrane of CE and RPE, and colocalizes and interacts with CTRP5 indicating a functional relationship between these two proteins.

The primary objective of this study was to compare the intraocular pressure (IOP)-lowering efficacy of travoprost 0.004%/timolol 0.5% fixed combination to the concomitant administration of travoprost 0.004% (TRAVATAN) and timolol 0.5% in subjects with open angle glaucoma or ocular hypertension.This was a randomized, multicenter, double-masked, active-controlled, parallel group study. Three hundred sixteen patients with open angle glaucoma or ocular hypertension were randomly assigned to travoprost 0.004%/timolol 0.5% ophthalmic solution fixed combination once daily in the morning or concomitant administration of timolol 0.5% once daily in the morning and travoprost 0.004% ophthalmic solution once daily in the evening. The efficacy and safety of the fixed combination were compared with concomitant therapy over three months. The primary efficacy outcome measure was mean intraocular pressure.Both travoprost 0.004%/timolol 0.5% fixed combination and the concomitant administration of travoprost 0.004% and timolol 0.5% produced statistically significant reductions from baseline in IOP, with mean IOP ranging from 15.2 to 16.5 mm Hg in the patients using travoprost 0.004%/timolol 0.5% fixed combination compared with 14.7 to 16.1 mm Hg in the concomitant group. The upper 95.1% confidence limit for the differences in mean IOP (fixed combination minus concomitant) wasor =1.5 mm Hg at 7 of 9 visits, including all three 8 AM time points, 24-hours post-dose. Mean IOP reductions from baseline ranged from 7.4 to 9.4 mm Hg in the fixed combination group compared with 8.4 to 9.4 mm Hg with concomitant therapy. Safety analysis demonstrated equivalent safety between the two treatment groups.A fixed combination of travoprost 0.004% and timolol 0.5% produced clinically relevant IOP reductions in patients with open angle glaucoma or ocular hypertension that were comparable to concomitant therapy with its components. Safety and tolerability of the fixed combination were also equivalent to concomitant therapy. Travoprost 0.004%/timolol 0.5% fixed combination offers IOP reduction equivalent to concomitant therapy, with potential benefits that include convenience (fewer bottles and drops per day), improved compliance, cost savings (based on fewer co-payments), and elimination of potential washout effects.

To investigate the effect of the timing of the scleral flap suture release on the safety and long-term success of phacotrabeculectomy.Retrospective, nonrandomized chart review.We studied 173 eyes of 173 consecutive patients who underwent primary phacotrabeculectomy, with or without intraoperative mitomycin-C, and subsequent scleral flap suture release.Early suture release (3 weeks) had a lower long-term success rate than late suture release (3 weeks), with an average follow-up period of 44.8 months. Patients who used mitomycin-C had statistically later suture release than did patients without mitomycin-C. There were nine cases of hypotony, for which independent risk factors were early suture release and the use of mitomycin-C.Greater long-term success with minimal complications was achieved when scleral flap suture release was performed three weeks after phacotrabeculectomy. Suture release within three weeks after surgery was associated with an increased risk of filtration failure and a higher risk of postoperative complications.

To compare the intraocular pressure (IOP) reduction between dorzolamide 2% and brimonidine 0.2% in primary open-angle glaucoma (POAG) or ocular hypertension (OHT).This study was a prospective, double-masked, randomized, crossover comparison of dorzolamide 2% (Trusopt) and brimonidine 0.2% (Alphagan), three times daily during two six-week study periods. The primary endpoint was mean change from baseline in trough IOP and secondary endpoints were mean change from baseline in IOP one and three hours after dosing. T-tests and a repeated-measures ANOVA were used to statistically evaluate the data.Of 43 patients enrolled, 41 completed the first treatment and 38 completed both treatments. Baseline IOP for dorzolamide was 24.3 mm Hg and brimonidine, 24.6 mm Hg (P = 0.9). Mean IOP reduction at trough was similar for both agents, 3.0 mm Hg (P = 0.96). Reductions at one and three hours were comparable (P = ns). Both agents were well tolerated with adverse events consistent with the package inserts. Dorzolamide was associated with more frequent stinging (P = 0.017) and burning (P0.001), while brimonidine was associated with more frequent dry eye (P = 0.04).Dorzolamide and brimonidine, as monotherapy, produced equivalent IOP-lowering efficacy at trough and at one and three hours after instillation, and both were well tolerated.

PURPOSE The purpose of this study was to identify the molecular basis of the apical membrane K(+) conductance in native bovine retinal pigment epithelium (RPE). METHODS RT-PCR, Northern blot, and Western blot analyses were used to detect the expression of the inwardly rectifying K(+) (Kir) channel subunits Kir7.1 and Kir4.1 in native bovine RPE and neural retina. The distribution of Kir7.1 protein was determined in frozen sections of bovine retina-RPE-choroid by indirect immunofluorescence analysis. RESULTS RT-PCR analysis revealed Kir7.1 transcript in both RPE and neural retina, but Kir4.1 transcript only in the neural retina. In Northern blot analysis, Kir4.1 probe hybridized to an appropriately sized-transcript in neural retina but not in RPE. Kir7.1 probe hybridized to a major transcript of approximately 1.5 kb in both RPE and neural retina, but with greater expression in RPE. In Western blot analysis, Kir7.1 antibody recognized a major monomer of approximately 53 kDa in RPE, whereas Kir4.1 antibody recognized a monomer of approximately 60 kDa in neural retina but not in RPE. Intense Kir7.1 immunolabeling was present on the apical surface of all RPE cells and appeared to extend over the length of the apical processes. Na(+),K(+)-ATPase expression varied among RPE cells, but in highly expressing cells, it colocalized with Kir7.1. CONCLUSIONS These results indicate that the Kir7.1 channel subunit, but not Kir4.1, is a major component of the apical K(+) conductance in bovine RPE. Kir7.1 is distributed over the length of apical processes, where it probably functions in the regulation of K(+) transport and the electrical response of the RPE to light-evoked changes in subretinal K(+) concentration.

Purpose To compare the long-term success rate of selective laser trabeculoplasty (SLT) versus argon laser trabeculoplasty (ALT). Design Retrospective chart review. Participants One hundred ninety-five eyes of 195 patients with uncontrolled open-angle glaucoma (OAG), of which 154 eyes underwent ALT and 41 eyes underwent SLT and were followed up for a maximum of 5 years. Intervention The SLT patients were treated with the frequency-doubled q-switched neodymium:yytrium–aluminum–garnet laser (532 nm). Approximately 50 to 55 nonoverlapping spots were placed over 180° of the trabecular meshwork at energy levels ranging from 0.6 to 1.0 mJ per pulse. The ALT patients were treated with the argon blue–green laser with between 45 to 55 adjacent, nonoverlapping spots over 180° of the trabecular meshwork at 470 to 1150 mW of energy per pulse. Main outcome measures The success rates were defined by criterion I and criterion II. Success by criterion I was defined as a decrease in intraocular pressure (IOP) of 3 mmHg or more with no additional medications, laser, or glaucoma surgery. Criterion II had the same requirements as criterion I, except that a 20% or more IOP reduction was required for success. Results The mean follow-up time was 37.4±14.7 months for patients in the SLT group and 33.6±17.0 months for patients in the ALT group. The long-term success rate was not significantly different between the ALT and SLT groups by either criterion (Kaplan-Meier survival analysis log-rank P = 0.20 by criterion I and P = 0.12 by criterion II). When comparing patients with and without previous ALT, there was not a statistically significant difference in the patients treated with SLT by either criterion (log-rank P = 0.37 by criterion I and P = 0.39 by criterion II). Conclusions In eyes with primary OAG that are receiving maximally tolerated medical therapy, SLT was found to be as effective as ALT in lowering IOP over a 5-year period. However, long-term data reveal that many of the glaucoma patients treated with SLT and ALT required further medical or surgical intervention. Whether SLT has better long-term success than ALT in repeat laser trabeculoplasty treatments remains unclear.

· Purpose: To evaluate the long-term effect of adjunctive subconjunctival 5-fluorouracil (5-FU) on the filtration outcome of primary glaucoma triple procedure (PGTP) in primary open-angle glaucoma (POAG) patients. · Methods: Seventy-four POAG patients were randomly assigned to PGTP alone (36 patients) or PGTP with adjunctive subconjunctival 5-FU (5.0 ± 1.3 injections of 5 mg each, total of 24.8 mg) (38 patients). After surgery, the patients were examined at regular intervals for intraocular pressure (IOP), visual acuity, medical therapy requirements, and complications. Surgical success was defined as IOP ≤20 mmHg on postoperative medication ≤1 without additional glaucoma surgery. · Results: Over an average follow-up (±SD) of 45.3 ± 25.0 months, both 5-FU and control groups maintained significant improvement of IOP control and visual acuity. However, there were no statistically significant differences between the 5-FU and control groups with respect to postoperative IOP, number of glaucoma medications, visual acuity outcome, and success rate overall or in selected patients with one or more of the risk factors for filtration failure. · Conclusions: The use of low-dose subconjunctival 5-FU (mean dosage of 24.8 mg in 5.0 ± 1.3 injections) as an adjunct did not significantly improve the long-term filtration outcome of PGTP in POAG patients.

To determine the efficacy and safety of limbus-based vs fornix-based conjunctival flaps in patients with primary open-angle glaucoma undergoing trabeculectomy combined with phacoemulsification and intraocular lens implantation with adjunctive subconjunctival mitomycin C.In a prospective study, 69 eyes of 69 patients with primary open-angle glaucoma, visually symptomatic cataracts, and no previous incisional ocular surgery were randomly assigned to limbus-based and fornix-based conjunctival flap groups. All patients received trabeculectomy combined with phacoemulsification and posterior chamber lens implantation with 1-minute (0.5 mg/ ml) application of subconjunctival mitomycin C.The mean intraocular pressures were significantly (P.05) lower on significantly (P.05) fewer medications postoperatively at 1 week, 1 month, 3, 6, 9, 12, and 15 to 18 months, and at last follow-up in both groups than they had been preoperatively. However, there were no significant (P.05) differences in postoperative mean intraocular pressure, mean number of medications, and visual acuity between the two groups at any time interval. Hypotony with wound leak was significantly (P = .019) higher in the limbus-based group. Other postoperative complications were not significantly (P.05) different between the two groups.There was no notable difference in glaucoma control or visual outcome between limbus-based and fornix-based conjunctival flaps in primary trabeculectomy combined with phacoemulsification and lens implantation with adjunctive subconjunctival mitomycin C. The fornix-based flap was as safe as, if not safer than, the limbus-based flap in the glaucoma triple procedure with adjunctive subconjunctival mitomycin C.

To evaluate the potential benefit of adjunctive subconjunctival mitomycin in patients with primary open-angle glaucoma undergoing primary trabeculectomy combined with phacoemulsification and intraocular lens implantation.Seventy-eight eyes of 78 patients with primary open-angle glaucoma with visually symptomatic cataracts and no previous incisional surgery were randomized to receive either no mitomycin C or a subconjunctival application of 1-, 3-, or 5-minute mitomycin C (0.5 mg/ml).Follow-up (mean +/- standard deviation) was 21.0 +/- 7.7 months. The mean postoperative intraocular pressures were significantly lower with significantly less medications than the preoperative values at each follow-up time (1, 3, 6, 9, 12, 15 months, and last follow-up) for all groups (P0.05 for each). However, there was no significant difference at each follow-up time in intraocular pressure, medications, or best-corrected visual acuity among the four groups or between the control and the total mitomycin C group.Adjunctive subconjunctival mitomycin C did not further improve the final intraocular pressure outcome of the primary trabeculectomy combined with phacoemulsification and intraocular lens implantation in patients with primary open-angle glaucoma. Future studies will determine the appropriate role, if any, for adjunctive mitomycin C in selected primary glaucoma triple procedures.

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.

Extracellular adenosine triphosphate (ATP) acts as a key signaling molecule in numerous cellular processes and is viewed as an endogenous danger signal released in large quantities by cells after inflammation, oxidative stress, and cell injury.1,2 It activates a class of cell-surface nucleotide receptors termed P2 receptors that are further categorized into P2Y receptors and P2X receptors.3 P2 receptors are widely expressed in excitable and nonexcitable cells, where they play important functions.4–8 P2Y receptor expression and function have been reported in human, rat, bovine, and rabbit retinal pigment epithelium (RPE).9–18 Little is known of P2X receptors in the RPE. Ryan et al.13 suggested that in addition to P2Y receptors, cultured rat RPE cells exhibited functional P2X receptors. Dutot et al.19 showed that ATP and a selective P2X7 agonist 2′,3′-O-(4-benzoylbenzoyl)-ATP (BzATP) stimulated YO-PRO-1 dye uptake and confocal immunofluorescence microscopy detected P2X7 receptor protein in a human RPE cell line, ARPE-19 cells. Among seven P2X receptors, the P2X7 receptor is unique because it plays a critical role in oxidative stress, cell death, and inflammation as well as in several diseases such as Alzheimer's disease and kidney diseases.20,21 However, the role of this receptor in the RPE is unknown. Because oxidative stress, cell death, and inflammation are implicated in age-related macular degeneration (AMD) and apoptotic RPE death underlies AMD,22,23 we hypothesized that ATP may induce RPE apoptosis by activation of the P2X7 receptor. By combining molecular, functional, and pharmacologic approaches, we show that the P2X7 receptor is expressed in native and cultured human RPE and that activation of the P2X7 receptor induces both Ca2+ signaling and apoptosis in RPE cells.

Objective To compare the intraocular pressure (IOP) responses of self-identified African American and white participants in the Ocular Hypertension Treatment Study to therapeutic trials of topical, nonselective β-adrenergic antagonists or prostaglandin analogues. Methods Multivariate models that adjusted for baseline IOP and corneal thickness were used to estimate IOP response by race. Participants included 536 who were prescribed topical β-adrenergic antagonists and 191 who were prescribed prostaglandin analogues, 25% of whom were African American. Main Outcome Measure Intraocular pressure response in the ipsilateral eye after 4 to 6 weeks of a therapeutic trial. Results Intraocular pressure response to nonselective β-adrenergic antagonists did not differ between African American and white participants. Intraocular pressure response to prostaglandin analogues was slightly greater in African American participants, but this difference was not statistically significant. With both classes of medication, greater IOP reduction was associated with higher baseline IOP and thinner central corneal measurement. Conclusions We found no statistically significant differences in IOP response to topical, nonselective β-adrenergic antagonists or prostaglandin analogues between self-identified African American and white individuals. Application to Clinical Practice Studies of IOP response to medication should statistically adjust for baseline IOP and central corneal thickness. Clinicians should consider factors other than ethnicity when choosing an ocular hypotensive medication for a patient. Trial Registration clinicaltrials.gov Identifier:"http://clinicaltrials.gov/ct/show/NCT00000125"

To evaluate whether baseline visual field data and asymmetries between eyes predict the onset of primary open-angle glaucoma (POAG) in Ocular Hypertension Treatment Study (OHTS) participants.A new index, mean prognosis (MP), was designed for optimal combination of visual field thresholds, to discriminate between eyes that developed POAG from eyes that did not. Baseline intraocular pressure (IOP) in fellow eyes was used to construct measures of IOP asymmetry. Age-adjusted baseline thresholds were used to develop indicators of visual field asymmetry and summary measures of visual field defects. Marginal multivariate failure time models were constructed that relate the new index MP, IOP asymmetry, and visual field asymmetry to POAG onset for OHTS participants.The marginal multivariate failure time analysis showed that the MP index is significantly related to POAG onset (P0.0001) and appears to be a more highly significant predictor of POAG onset than either mean deviation (MD; P = 0.17) or pattern standard deviation (PSD; P = 0.046). A 1-mm Hg increase in IOP asymmetry between fellow eyes is associated with a 17% increase in risk for development of POAG. When threshold asymmetry between eyes existed, the eye with lower thresholds was at a 37% greater risk of development of POAG, and this feature was more predictive of POAG onset than the visual field index MD, though not as strong a predictor as PSD.The MP index, IOP asymmetry, and binocular test point asymmetry can assist in clinical evaluation of eyes at risk of development of POAG.

PURPOSE To report on a successful use of fascia lata patch graft in revision of trabeculectomy for management of severe chronic discomfort associated with an exuberant conjunctival filtering bleb over a very nasal filtering site. METHODS After dissecting a conjunctival flap over the area of the trabeculectomy at the nasal quadrant, fascia lata patch graft was sutured in place over the filtering site when primary suture closure was found ineffective. A new trabeculectomy was performed temporal and superior to the old site, and the conjunctival wound closed watertight. RESULTS The fascia lata patch graft was effective in closing the filtration over the old trabeculectomy site at the nasal quadrant, and a new filtering bleb developed superiorly over the new trabeculectomy site, resulting in sustained IOP control. CONCLUSION Fascia lata patch graft was effective in revision of trabeculectomy.

Ocular injuries caused by the inflation of driver- or passenger-side air bags during motor vehicle collisions are increasing in frequency. The literature contains several case reports of air bag-related ocular injuries. Two of these cases involve corneal injuries1,2and one describes vitreous and subretinal hemorrhages.3 Report of a Case. The cornea and glaucoma services of the Kresge Eye Institute of Wayne State University, Detroit, Mich, examined a 51-year-old female physician who had sustained severe anterior segment injury in her right eye as a result of a driver-side air bag discharge during a motor vehicle crash. While the details of the collision are not known, it is known that during the immediate postcollision period, the patient required hospitalization for 5 days for a hyphema. Treatment at that time included topical steroids and cycloplegics. Ocular examination of the right eye 1 year later revealed a best corrected visual acuity of

Transscleral suture fixation of posterior chamber lenses is a popular recent alternative for avoiding the potential complications of anterior chamber lenses and in the absence of sufficient iris support for an anterior chamber lens. If a posterior chamber lens is fixated by only two points in the ciliary sulcus, the lens may tilt relative to the visual axis, causing clinically significant and possibly uncorrectable astigmatism. Described methods of three- or four-point fixation are technically more difficult and can result in an improperly centered lens. A method is described herein that allows stable four-point fixation with precise lens placement using only two sutures. This method also allows the suture knot to be buried in the eye without the use of scleral flaps.