Reliability of Measurements Using Ocular Response Analyzer as a Screening Tonometer and Corneal Hysteresis Values in the Presence or Absence of Glaucomatous Changes in Fundus.

PRCIS: Use of the Ocular Response Analyzer (ORA) as a screening tonometer in clinical practice yielded reliable measurements in over 80% of eyes screened. Including corneal hysteresis (CH) data in screening may improve the accuracy of glaucoma detection. PURPOSE: To examine measurement reliability when the ORA is used as a screening tonometer, and to compare CH measurements in eyes with and those without glaucomatous changes in the fundus. PATIENTS AND METHODS: 1488 eyes of 747 patients (mean age: 53.5 ± 20.4 y, range: 6-94 y) underwent intraocular pressure (IOP) measurement using ORA as screening. The percentage of eyes with a waveform score ≥6, the recommended threshold indicating reliability, was calculated. Eyes that had waveform score ≥6 and had undergone fundus photography and optical coherence tomography were assessed for the presence or absence of glaucomatous changes in fundus from optical coherence tomography and fundus images, and CH was compared between the 2 groups. RESULTS: Mean ± SD (range) of ORA measurements were: Goldmann-correlated IOP 14.9 ± 4.8 (1.0-63.2) mm Hg, corneal-compensated IOP 16.2 ± 4.7 (3.2-73.6) mm Hg, CH 9.7 ± 1.5 (0.0-20.6) mm Hg, and waveform score 7.3 ± 1.5 (0.1-9.7). Eighty-four percent of eyes had a waveform score ≥6. Among 192 eyes (127 patients, aged 53.5 ± 18.0 y) with waveform score ≥6 and evaluable for glaucomatous changes in the fundus, 53 eyes were determined as positive and 139 eyes as negative. CH was 9.6 ± 1.4 (6.8-13.3) mm Hg in the positive group and 10.2 ± 1.2 (6.9-13.3) mm Hg in the negative group, and was significantly lower in the positive group ( P =0.003). CONCLUSION: When using ORA as a screening tonometer, reliable results were obtained in ~80% of the eyes. CH was lower in the glaucomatous change-positive group compared with the glaucomatous change-negative group, but the ranges overlapped between the 2 groups.

Machine Learning Approach for Intraocular Disease Prediction Based on Aqueous Humor Immune Mediator Profiles.

PURPOSE: Various immune mediators have crucial roles in the pathogenesis of intraocular diseases. Machine learning can be used to automatically select and weigh various predictors to develop models maximizing predictive power. However, these techniques have not yet been applied extensively in studies focused on intraocular diseases. We evaluated whether 5 machine learning algorithms applied to the data of immune-mediator levels in aqueous humor can predict the actual diagnoses of 17 selected intraocular diseases and identified which immune mediators drive the predictive power of a machine learning model. DESIGN: Cross-sectional study. PARTICIPANTS: Five hundred twelve eyes with diagnoses from among 17 intraocular diseases. METHODS: Aqueous humor samples were collected, and the concentrations of 28 immune mediators were determined using a cytometric bead array. Each immune mediator was ranked according to its importance using 5 machine learning algorithms. Stratified k-fold cross-validation was used in evaluation of algorithms with the dataset divided into training and test datasets. MAIN OUTCOME MEASURES: The algorithms were evaluated in terms of precision, recall, accuracy, F-score, area under the receiver operating characteristic curve, area under the precision-recall curve, and mean decrease in Gini index. RESULTS: Among the 5 machine learning models, random forest (RF) yielded the highest classification accuracy in multiclass differentiation of 17 intraocular diseases. The RF prediction models for vitreoretinal lymphoma, acute retinal necrosis, endophthalmitis, rhegmatogenous retinal detachment, and primary open-angle glaucoma achieved the highest classification accuracy, precision, and recall. Random forest recognized vitreoretinal lymphoma, acute retinal necrosis, endophthalmitis, rhegmatogenous retinal detachment, and primary open-angle glaucoma with the top 5 F-scores. The 3 highest-ranking relevant immune mediators were interleukin (IL)-10, interferon-γ-inducible protein (IP)-10, and angiogenin for prediction of vitreoretinal lymphoma; monokine induced by interferon γ, interferon γ, and IP-10 for acute retinal necrosis; and IL-6, granulocyte colony-stimulating factor, and IL-8 for endophthalmitis. CONCLUSIONS: Random forest algorithms based on 28 immune mediators in aqueous humor successfully predicted the diagnosis of vitreoretinal lymphoma, acute retinal necrosis, and endophthalmitis. Overall, the findings of the present study contribute to increased knowledge on new biomarkers that potentially can facilitate diagnosis of intraocular diseases in the future.

Absence of Posterior Vitreous Detachment Is a Risk Factor of Severe Bleb-Related Endophthalmitis.

PURPOSE: Bleb-related endophthalmitis (BRE) after glaucoma surgery is an infection caused by bacteria in the avascular bleb gaining access into the eye. We report the clinical features and outcome of 10 consecutive eyes with severe BRE treated at our hospital. METHODS: Ten patients (10 eyes) with stage IIIb BRE after trabeculectomy diagnosed and treated at the Department of Ophthalmology, Tokyo Medical University, between April 2013 and May 2015, were studied. Patient background, type of glaucoma, interval from the first trabeculectomy, pretreatment bleb findings, causative microorganisms, surgical methods, status of posterior vitreous detachment (PVD), and postoperative visual acuity were examined. RESULTS: The 10 patients comprised 8 males and 2 females, with mean age of 70.6 years at BRE onset. The types of glaucoma were open-angle glaucoma in 7 patients, neovascular glaucoma in 2, and secondary glaucoma in 1. All eyes underwent trabeculectomy combined with mitomycin C prior to the development of BRE. The interval from the first glaucoma surgery to onset of endophthalmitis was 8.5 ± 4.1 years. Examination of the bleb revealed leakage of aqueous humor from the avascular bleb in all eyes. Bacteria were isolated from intraocular samples of 8 eyes; namely, Viridans streptococci in 5 eyes, Staphylococcus epidermidis in 1, Branhamella catarrhalis in 1, and coagulase-negative Staphylococci in 1. BRE was treated by vitrectomy in 9 eyes and enucleation in 1 eye. PVD was produced intentionally during vitrectomy in 6 eyes. Histopathological examination of the enucleated eye showed no PVD. Visual acuity improved by 3 lines or more in 6 patients, while decimal visual acuity remained lower than 0.1 in 4 patients. CONCLUSION: BRE developed frequently in eyes with no PVD. The absence of PVD may be a risk factor of severe BRE.

Incidence of Postoperative Ptosis Following Trabeculectomy With Mitomycin C.

PURPOSE: To prospectively investigate the incidence of postoperative ptosis following trabeculectomy by comparing preoperative and postoperative margin reflex distance (MRD), and to analyze the clinical factors associated with ptosis. PATIENTS AND METHODS: Patients who underwent trabeculectomy with mitomycin C in unilateral eye between 2010 and 2012 were enrolled. MRD was measured before and 3 and 6 months after trabeculectomy. The MRD is the distance between the light reflex at central cornea and the upper eyelid margin when the patient gazed at a pen light placed 50 cm away straightly. Postoperative ptosis was defined as a decrease in MRD≥2 mm from preoperative level. The correlation among ΔMRD (difference between preoperative and 6 mo postoperative MRD) and clinical factors comprising age, spherical equivalent, preoperative MRD, 6-month postoperative intraocular pressure (IOP), and IOP reduction (difference between preoperative and 6 mo postoperative IOP) was analyzed. RESULTS: Thirty-six patients (36 eyes) were analyzed. Preoperative median MRD was not different between the operated eye and nonoperated fellow eye (both 4.0 mm, P=0.65). The 3- and 6-month postoperative MRD in the operated eye were significantly reduced compared with preoperative MRD (3.0 mm, P=0.04 and 2.5 mm, P=0.01, respectively). The 3- and 6-month postoperative MRD in the nonoperated eye were not different from preoperative MRD (4.0 mm, P=0.81 and 4.0 mm, P=0.85, respectively). The incidence of ptosis at 6 months after operation was 19% (7 of 36 eyes). The IOP was significantly decreased at 3 and 6 months after operation (both P<0.01). No correlation was observed between ΔMRD and all the factors analyzed. CONCLUSIONS: Ptosis is a major complication following trabeculectomy with mitomycin C, with an incidence of 19% at 6 months after operation.

Incidence of deepening of the upper eyelid sulcus after topical use of travoprost ophthalmic solution in Japanese.

PURPOSE: To investigate the incidence of deepening of the upper eyelid sulcus (DUES) with topical use of travoprost in Japanese glaucoma patients. PATIENTS AND METHODS: This prospective study enrolled 32 primary open-angle glaucoma Japanese patients who had been treated topically with travoprost unilaterally for 6 months at baseline, and started treatment in both eyes. The patients were observed during outpatient visits at 2, 4, and 6 months. At every visit, the photographs of both eyes and forehead were displayed randomly and the presence of DUES was diagnosed when 3 examiners unanimously rated the case as positive. The patients were also asked if they noticed any subjective symptom of DUES. Sex, refraction, and intraocular pressure (IOP) were evaluated as potential risk factors. RESULTS: DUES was identified objectively in 34% (11/32) of the patients after 2 months of treatment, and in 53% (17/32) after 4 and 6 months of treatment. The incidence was significantly higher in older patients (P<0.05), but not related to sex, refraction, pretreatment and posttreatment IOP, and IOP reduction. Finally, 41% (7/17) of patients with objectively diagnosed DUES noticed the presence of DUES by themselves. No patient dropped out of the study because of DUES. CONCLUSIONS: DUES is a common side effect of topical travoprost treatment in Japanese glaucoma patients.

Incidence of deepening of upper eyelid sulcus after topical use of tafluprost ophthalmic solution in Japanese patients.

PURPOSE: To investigate the incidence of deepening of upper eyelid sulcus (DUES) with topical use of tafluprost in Japanese glaucoma patients. METHODS: This study was a prospective, open-label, non-controlled case series conducted at a single center. Thirty-six primary open-angle glaucoma Japanese patients who had no history of surgery were enrolled. The patients were prescribed 0.0015% topical tafluprost once daily to one eye that had the more severe visual field disorder, and observed during outpatient visits before and at 30, 60, and 90 days after starting treatment. At every visit, three examiners judged the presence of DUES unanimously by facial photographs including eyebrows and lower eyelids. The primary outcome variable was the incidence of DUES at the end of day 90 in the study as assessed by observer-masked facial photography. The patients were also asked if they noticed any subjective symptom of DUES. Gender, refraction, and intraocular pressure were evaluated as potential risk factors. RESULTS: Thirty-two patients completed this clinical trial. DUES were identified objectively in 19% (6/32) of the patients after 90 days of treatment. The incidence was not related to gender, refraction, baseline or post-treatment intraocular pressure, or intraocular pressure reduction. Finally, 17% (1/6) of patients with objectively diagnosed DUES noticed the presence of DUES by themselves. No patient dropped out of the study because of DUES. CONCLUSION: Similar to other prostaglandin analogs, topical use of tafluprost ophthalmic solution is associated with DUES as a local adverse reaction.

Human iris pigment epithelial cells suppress T-cell activation via direct cell contact.

The purposes of the present study were to investigate whether cultured human iris pigment epithelial (hIPE) cells acquire the ability to modify T-cell activation, and if so, to identify the mechanism. Human IPE cells were prepared from patients who underwent glaucoma surgery, and were cultured in RPMI 1640 medium containing 10% fetal calf serum for 4-7 days. Expression of MHC molecules and co-stimulatory molecules on cultured hIPE cells either unstimulated or stimulated with IFN-gamma was examined by FACS. In addition, peripheral blood T cells were incubated with cultured hIPE cells prepared from the same patients and anti-CD3 antibody in a transwell culture system, or in the presence of anti-PD-L1 and PD-L2 antibodies, and T cell proliferation was assessed by [3H]-thymidine incorporation. The hIPE cells inhibited anti-CD3-driven T-cell activation but the inhibition was diminished when tested in the transwell culture system, indicating that a contact-dependent mechanism is important in the immunoregulatory roles of hIPE. Although cultured hIPE cells expressed Class I and PD-L1 but not Class II or PD-L2, all these molecules were observed on hIPE cells cultured in the presence of IFN-gamma. Blocking antibodies against both PD-L1 and PD-L2 reduced the immunoregulatory activity of hIPE cells. Our data indicates that cultured hIPE cells inhibit T-cell activation by T-cell receptor ligation, which is mediated by cell-to-cell contact in part via the PD-L1 and PD-L2 pathways.

Efficacy and safety of transconjunctival scleral flap resuturing for hypotony after glaucoma filtering surgery.

BACKGROUND: To evaluate the efficacy and safety of transconjunctival scleral flap resuturing for the management of hypotony-associated excess filtration after glaucoma filtering surgery. METHODS: Fifty-six eyes of 55 patients with hypotony maculopathy and/or choroidal detachment caused by excess filtration after glaucoma filtering surgery underwent transconjunctival scleral flap resuturing directly through the conjunctiva, using a 10-0 nylon suture with a round tapered needle. Intraocular pressure (IOP) after suture, best-corrected visual acuity, rate of resolution of hypotony maculopathy and choroidal detachment, rate of complication, and rate of supplemental surgical treatment were assessed. RESULTS: IOP (mean +/- SD) was 2.9 +/- 1.4 mmHg before suture, and elevated significantly to 7.3 +/- 4.5 mmHg at 1 week after suture, 7.2 +/- 3.5 mmHg at 1 month, 8.4 +/- 4.1 mmHg at 1 year, and 8.1 +/- 3.5 mmHg at the last follow-up (mean of 23 months). The best-corrected visual acuity was improved. Hypotony maculopathy was resolved in 92% and choroidal detachment in 100% of the patients. None of the patients required supplemental surgical treatment, because transconjunctival scleral flap resuturing failed to increase IOP. Suture removal was performed in 14 eyes that showed high IOP after suture. Of these eyes, six required needle revision and one required surgical bleb revision. In two eyes, aqueous humor leak after suture was controlled by wearing contact lenses. No bleb-associated infection was observed. CONCLUSION: Even though additional treatments such as repeated suture, suture removal, and needle revison were necessary in some cases, transconjunctival scleral flap resuturing is a simple and minimally invasive procedure that improves hypotony after glaucoma filtering surgery, with no serious complication.

Additive effect of dorzolamide or carteolol to latanoprost in primary open-angle glaucoma: a prospective randomized crossover trial.

PURPOSE: To compare the additive effect of dorzolamide or carteolol to latanoprost on intraocular pressure (IOP) in glaucoma patients. DESIGN: Prospective open-label randomized crossover clinical study. METHODS: A total of 64 patients with primary open-angle glaucoma were treated with latanoprost 0.005% once daily for 3 months then randomized to receive latanoprost plus dorzolamide 1% 3 times daily (dorzolamide preceding group; n=32) or carteolol hydrochloride 2% twice daily (carteolol preceding group; n=32) for a further 3 months. Then, all patients were crossed over to the opposite treatment arm for a further 3 months. IOP was recorded each month at around the time same as on the baseline day. RESULTS: Sixty-one patients (95%) completed this trial. In the dorzolamide preceding group, mean (+/-SD) IOP was 19.0+/-2.1 mm Hg at baseline and 16.0+/-2.1 mm Hg at the end of latanoprost monotherapy (P<0.01). Addition of dorzolamide reduced IOP to 15.0+/-1.3 mm Hg and this was not changed by switching to carteolol (15.1+/-1.7 mm Hg). In the carteolol preceding group, IOP was 19.1+/-1.9 mm Hg at baseline and 16.2+/-1.2 mm Hg at the end of latanoprost monotherapy (P<0.01). Addition of carteolol reduced IOP to 14.9+/-1.5 mm Hg, and after switching to dorzolamide IOP was 15.2+/-1.5 mm Hg. Mean additional IOP reduction was 0.9+/-1.2 mm Hg (5.6%) for the latanoprost-dorzolamide combination and 1.1+/-1.5 mm Hg (6.8%) for the latanoprost-carteolol combination. Hence, IOP reduction by carteolol and dorzolamide additionally to latanoprost was not different. CONCLUSIONS: Both dorzolamide and carteolol reduce IOP additively when used in combination with latanoprost, and the additive effect of these drugs is equal.

Comparison of the additive effects of nipradilol and carteolol to latanoprost in open-angle glaucoma.

PURPOSE: To compare the effects of nipradilol and carteolol on intraocular pressure (IOP) when added to latanoprost treatment for glaucoma patients. METHODS: Fifty patients with primary open-angle glaucoma were treated with latanoprost 0.005% once daily for 3 months. Then they were assigned to one of two groups randomly. One group received nipradilol 0.25% twice daily (nipradilol preceding group; n = 25), and the other carteolol hydrochloride 2% twice daily (carteolol preceding group; n = 25), for 3 months in addition to latanoprost. Then, nipradilol and carteolol were switched, and the subjects were treated for 3 more months. One eye was selected randomly for analysis. RESULTS: In the nipradilol preceding group, IOP was 21.4 +/- 2.3 mmHg (mean +/- SD) at baseline, and 16.8 +/- 1.9 mmHg at the end of latanoprost monotherapy (P < 0.01). The addition of nipradilol decreased IOP to 15.8 +/- 1.7 mmHg, and the change to carteolol, to 15.3 +/- 2.0 mmHg. In the carteolol preceding group, IOP was 21.2 +/- 2.0 mmHg at baseline, and 17.0 +/- 2.1 mmHg at the end of latanoprost monotherapy (P < 0.01). The addition of carteolol decreased IOP to 15.4 +/- 1.8 mmHg, and the change to nipradilol, to 16.3 +/- 1.9 mmHg. Additional IOP reduction was greater with carteolol than with nipradilol (cross-over analysis of variance; P = 0.0005). CONCLUSIONS: Both nipradilol and carteolol have additive effects when used in combination with latanoprost. Carteolol, however, may have a more potent effect than nipradilol.

Conjunctival flora in patients with human immunodeficiency virus infection.

PURPOSE: To compare the conjunctival flora of human immunodeficiency virus (HIV)-positive and HIV-negative patients. Also, to assess the prophylactic effect of oral clarithromycin against Mycobacterium avium complex on the conjunctival flora of HIV-positive patients. METHODS: Ninety-four eyes of 47 HIV-positive patients and 122 eyes of 61 control patients were examined. All participants had a detailed anterior segment examination, including conjunctival cultures and laboratory blood tests. Culture results for different organisms were evaluated by chi-square analysis between the groups. The effect of systemic antibiotic treatment on the conjunctival flora of patients with HIV infection was evaluated by chi-square analysis. RESULTS: Bacterial organisms in the conjunctival sac were detected in four out of 28 (14.3%) eyes of HIV-positive patients treated with systemic clarithromycin and in 32 out of 66 (48.5%) eyes of HIV-positive patients without systemic clarithromycin treatment (p < 0.01). The CD4-positive T-cell counts in these groups were 158/microl and 416/microl, respectively (p < 0.01). Bacterial organisms were also detected in 46 of 122 (37.7%) control eyes. No difference was observed in the types and proportions of organisms isolated from the conjunctiva between HIV-positive patients without systemic clarithromycin treatment and controls. CONCLUSION: There was no difference between the conjunctival flora of HIV-negative and HIV-positive patients. Systemic clarithromycin treatment decreased the conjunctival flora of HIV patients, including those who had a CD4 count that was less than 50/microl.

Resuturing the scleral flap through conjunctiva for treatment of excess filtration.

PURPOSE: To elevate the intraocular pressure (IOP) in eyes with persistent hypotony caused by excess filtration after trabeculectomy. DESIGN: Interventional case series. METHODS: The scleral flap was sutured directly through the conjunctival flap using a round, tapered needle with a 10-0 nylon suture. This procedure has been performed in 10 eyes. RESULTS: The IOP elevated from 2.6 (+/- 1.0) mm Hg to 8.8 (+/- 3.7) mm Hg in 1 week and has been maintained between 6 to 14 mm Hg during the follow-up. Hypotony maculopathy has disappeared in nine eyes. The suture was buried in the conjunctiva spontaneously in 1 week in all cases. No complications developed. CONCLUSIONS: Suturing the scleral flap directly through the conjunctival flap is a simple and effective modality to treat the hypotony caused by excess filtration after trabeculectomy.