Evaluation of the association between macular damage and disability glare in patients with advanced glaucoma.

PURPOSE: This study aimed to investigate the factors associated with disability glare in patients with advanced glaucoma and evaluate the impact of disability glare on the vision-related quality of life. METHODS: We prospectively studied 225 eyes (225 patients) with advanced glaucoma. The visual function was evaluated using the 10-2 and 24-2 Humphrey visual field (VF) (Dublin, California) and contrast sensitivity test. Structural parameters were obtained using RTVue optical coherence tomography and angiography (Fremont, California). Significant loss of macular vessel density (mVD) was defined as VD < 30%. Each participant completed the National Eye Institute Visual Function Questionnaire 25 (NEI-VFQ-25) and questions regarding subjective symptoms of glare. RESULTS: Fifty-six patients (24.9%) experienced glare and had a lower NEI-VFQ-25 composite score (P = 0.017). The average retinal nerve fiber layer and ganglion cell complex thickness and mean deviation (MD) in the 24-2 VF test were not associated with glare. Significant superior or inferior mVD loss (P < 0.001; odds ratio [OR], 3.45; and 95% confidence interval [CI], 1.83-6.55), lower logarithmic contrast sensitivity at 0.75 cycles/degree (P < 0.001; OR, 0.27; and 95% CI, 0.13-0.56), and worse MD in the 10-2 VF test (P < 0.001; OR, 0.93; and 95% CI, 0.89-0.97) showed an association with glare. CONCLUSION: In advanced glaucoma, central VF defect and mVD loss are associated with disability glare, which negatively impacts vision-related quality of life.

Relationship of axial length and corneal biomechanical properties with susceptibility to unilateral normal-tension glaucoma.

PURPOSE: Corneal biomechanics, reflecting structural vulnerabilities of the eyeball, may participate in the pathogenesis of unilateral normal-tension glaucoma. This study investigated the pathophysiology of unilateral normal-tension glaucoma using Corvis ST (OCULUS Optikgeräte GmbH) and other ocular characteristics. METHODS: Eighty-three patients with normal-tension glaucoma with unilateral visual field loss and structurally unaffected fellow eyes and 111 healthy controls were included in this prospective study. Dynamic corneal response parameters, intraocular pressure measured by rebound tonometry, central corneal thickness, and axial length were assessed on the same day. Measurements were compared between affected eyes, unaffected fellow eyes, and control eyes. Risk factors for normal-tension glaucoma and unilateral involvement were the main outcome measures. RESULTS: A shorter first applanation time (adjusted odds ratio, 0.061; 95% confidence interval, 0.018-0.215) and a larger peak distance (adjusted odds ratio, 4.935; 95% confidence interval, 1.547-15.739) were significant risk factors for normal-tension glaucoma and were associated with greater glaucoma severity (both P < 0.001). Axial length (adjusted odds ratio, 29.015; 95% confidence interval, 4.452-189.083) was the predominant risk factor for unilateral involvement in patients with normal-tension glaucoma. CONCLUSION: The eyes with normal-tension glaucoma were more compliant than healthy eyes. Axial elongation-associated optic nerve strain may play an important role in unilateral normal-tension glaucoma with similar corneal and scleral biomechanics in both eyes.

Evolution of the Prevalence of Myopia among Taiwanese Schoolchildren: A Review of Survey Data from 1983 through 2017.

PURPOSE: The aim of this study was to evaluate the changes in the prevalence of myopia in Taiwanese schoolchildren over the past few decades and to analyze the risk factors for myopia. DESIGN: Analysis of 8 consecutive population-based myopia surveys conducted from 1983 through 2017. PARTICIPANTS: An average of 8917 (5019-11 656) schoolchildren 3 to 18 years of age were selected using stratified systematic cluster sampling or by probability proportional to size sampling. METHODS: All participants underwent complete ophthalmic evaluations. Three drops of 0.5% tropicamide were used to obtain the cycloplegic refractive status of each participant. Questionnaires were used to acquire participant data from the 1995, 2005, 2010, and 2016 surveys. MAIN OUTCOME MEASURES: Prevalence of myopia (spherical equivalence of ≤-0.25 diopter [D]) and high myopia (≤-6.0 D) was assessed. Multivariate analyses of risk factors were conducted. RESULTS: The prevalence of myopia among all age groups increased steadily. From 1983 through 2017, the weighted prevalence increased from 5.37% (95% confidence interval [CI], 3.50%-7.23%) to 25.41% (95% CI, 21.27%-29.55%) for 7-year-olds (P = 0.001 for trend) and from 30.66% (95% CI, 26.89%-34.43%) to 76.67% (95% CI, 72.94%-80.40%) for 12-year-olds (P = 0.001 for trend). The prevalence of high myopia also increased from 1.39% (95% CI, 0.43%-2.35%) to 4.26% (95% CI, 3.35%-5.17%) for 12-year-olds (P = 0.008 for trend) and from 4.37% (95% CI, 2.91%-5.82%) to 15.36% (95% CI, 13.78%-16.94%) for 15-year-olds (P = 0.039 for trend). In both the 2005 and 2016 survey samples, children who spent less than 180 minutes daily on near-work activities showed significantly lower risks for myopia developing (<60 minutes: odds ratio [OR], 0.48 and 0.56; 60-180 minutes: OR, 0.69 and 0.67). In the 2016 survey, spending more than 60 minutes daily on electronic devices was associated significantly with both myopia and high myopia (OR, 2.43 and 2.31). CONCLUSIONS: The prevalence of myopia among schoolchildren increased rapidly from 1983 through 2017 in Taiwan. The major risk factors are older age and time spent on near-work activities. Use of electronic devices increased the amount of time spent on near-work and may increase the risk of developing myopia.

Exploring a peptidomimetic approach of N-cadherin in modulating fibroblast growth factor receptor signaling for corneal endothelial regeneration.

Endothelial rejection and a critical shortage of corneal transplants present an unmet medical need in corneal regeneration research area. Although basic fibroblast growth factor (bFGF) is a potent mitogenic factor for corneal ex vivo expansion, it is also a morphogen eliciting unfavorable endothelial-mesenchymal transition (EnMT) of corneal endothelial cells. A pharmacological reagent that retains the beneficial proliferative effect while lacking the EnMT effect of bFGF would be of great potential in corneal regeneration. In present study, we demonstrated that bFGF not only activated the canonical fibroblast growth factor receptor 1 (FGFR1) tyrosine kinase pathway, but also further upregulated matrix metalloproteinase activity to cleave N-cadherin into N-terminus and C-terminus fragments, which activated the classical FGFR1 tyrosine kinase pathway and a cryptic ß-catenin pathway to affect corneal proliferation and EnMT, respectively. We generated the synthetic peptides resembling a critical motif in the ectodomain of N-cadherin and found these peptides enhanced downstream proliferative signaling of FGFR1 but without seemingly EnMT effect. The potential of these peptides can be demonstrated on both ex vivo cell culture and in vivo rat cryo-injury model. Our study indicated this peptidomimetic approach of N-cadherin can stimulate corneal regeneration and offer a promising therapeutic option to treat corneal endothelial dysfunction.

Assessment of ocular surface disease in glaucoma patients with benzalkonium chloride-preserved latanoprost eye drops: a short-term longitudinal study.

PURPOSE: To prospectively evaluate the effect of benzalkonium chloride (BAK)-preserved latanoprost on ocular surface damage and identify the associated risk factors among treatment-naive glaucoma patients. METHODS: The basal Schirmer's test results, corneal Oxford staining score, non-invasive keratograph tear-breakup time, oculus hyperemia index score (objective metrics), and ocular surface disease index (OSDI) questionnaire (subjective metric) were evaluated at baseline, 1 month, and 4 months after receiving latanoprost eye drops. Associated risk factors were assessed by multivariate linear regression. RESULTS: Seventy-four eyes (44 patients) were enrolled. Basal Schirmer's test tear-flow and Oxford scores gradually deteriorated (ß = -0.14, P = 0.001 and ß = 0.1, P < 0.001, respectively). The percentage of unstable tear-film (breakup time < 10 s) increased significantly at 4 months (6.21% vs 9.11%, P = 0.042). Hyperemic scores increased significantly at 1 month and normalized at 4 months (P = 0.01 and P = 0.16, respectively); total OSDI scores tended to improve (ß = -0.76, P = 0.06). Older age was associated with additional corneal Oxford staining (P = 0.005); female sex was associated with increased unstable tear-film scores (P = 0.01). Artificial tear use was associated with a smaller decrease in basal Schirmer's test values (P = 0.01) and a smaller increase in unstable tear-film scores (P = 0.02). CONCLUSIONS: Preserved latanoprost eye drops affected ocular surface changes in glaucoma patients through decreased basal tear secretion. Artificial tears represent an early intervention in vulnerable glaucoma patients with reduced tear secretion and impaired tear-film stability.

Long-term structural and functional outcomes of primary congenital glaucoma.

PURPOSE: To investigate the clinical characteristics and long-term outcomes of primary congenital glaucoma (PCG) patients. METHODS: In this retrospective, longitudinal, cohort study, PCG patients with reliable visual field (VF) tests and optical coherence tomography (OCT) were included. Disease progression was detected using guided progression analysis with OCT and the change analysis of mean deviation (MD) slope with VF tests. Factors associated with the disease progression and visual prognosis were analyzed. RESULTS: Twenty-nine eyes from 11 bilateral and 7 unilateral PCG patients were enrolled. LogMAR visual acuity declined (0.15 vs. 0.40, P < 0.001). The change rate of the average retinal nerve fiber layer thickness was - 0.83 ± 1.45 µm/year, and 28% of eyes showed glaucoma progression on OCT. The median of the MD slope was 0.16 (- 1.19 to 1.07) dB/year, and 14% of eyes showed glaucoma progression on the VF test. Higher average intraocular pressure (IOP) (P = 0.046) and IOP fluctuation (P = 0.031) predicted disease progression. None of the fellow eyes of unilateral PCG patients developed glaucoma during the follow-up. At last, 59% of eyes had visual acuity > 20/70, and 31% had MD > - 6 dB. Patients with worse baseline visual acuity (P = 0.027), worse baseline MD (P < 0.001), and smaller neuroretinal rim area (P < 0.001) showed worse final MD values. CONCLUSIONS: Aggressive IOP control is necessary to prevent structural and functional decline in PCG patients. Their fellow eyes are not at risk of glaucoma. Baseline neuroretinal rim area can predict the functional outcome.

Refractive outcomes of cataract surgery in patients receiving trabeculectomy-a comparative study of combined and sequential approaches.

BACKGROUND: Cataract surgery in combination with or after trabeculectomy is often required for improving vision in glaucoma patients. Intraocular pressure (IOP) changes may influence refractive outcomes after cataract surgery. We compared refractive outcomes of the combined and sequential approaches in managing glaucoma and cataract. METHODS: This retrospective case-control study included 52 patients (57 eyes) who underwent phacotrabeculectomy (combined group) and 39 patients (42 eyes) who underwent phacoemulsification at least three months post-trabeculectomy (sequential group). The IOP and refraction prediction error were compared at three months after cataract surgery. Univariate regression analyses were used to assess risk factors for the postoperative refraction prediction error. RESULTS: Anti-glaucomatous medications were not administered to either group. The mean postoperative IOP (12.96 vs. 13.80 mmHg; P = .392), refraction prediction error (-0.32 ± 1.53 vs. -0.47 ± 1.14 D, P = .594), mean absolute error (1.02 ± 1.18 vs. 0.8 ± 0.93 D, P = .320), and surgically induced astigmatism (1.85 ± 1.40 vs. 2.16 ± 1.16 D, P = .161) did not differ significantly between the combined and sequential groups. In the sequential group, the refraction prediction error correlated to the IOP change, with a 1-mm Hg rise resulting in a -0.07-diopter shift between the expected and observed refraction (r = -0.380, R2 = 0.144, P = .013); no such correlation was observed in the combined group. CONCLUSION: Both approaches resulted in similar effective IOP control and accurate intraocular lens predictability. The IOP change affected the postoperative refraction prediction error only in the sequential approach.

Clinical characteristics of glaucoma patients with disc hemorrhage in different locations.

PURPOSE: To compare the clinical characteristics and outcomes of eyes with unilateral disc hemorrhage (DH) in different locations. METHODS: This was a retrospective cohort study. DHs were classified by locations: the superior, superotemporal, inferotemporal, or inferior sectors of optic disc were classified as the susceptible area, while other sectors were defined as the less susceptible area. Structural and functional outcomes were analyzed by the Humphrey field analyzer and spectral domain optical coherence tomography. RESULTS: Forty-three eyes with DHs in the susceptible area were less myopic and had more peripapillary-type DH, larger cup-to-disc ratio, cup volume, and disc area. Thirty-three eyes with DHs in the less susceptible area had less association with RNFL defects, greater tilted ratio, and less torsion of the disc. Follow-up revealed that the change in sectoral RNFL (µm) thickness was significantly greater for DHs in the susceptible area within one year (- 6.0 ± 14.0 vs. 0.7 ± 13.0, p = 0.035) and two years (- 10.0 ± 17.4 vs. - 1.1 ± 7.6, p = 0.012), while the change in average RNFL thickness was not different. Eyes with DHs in the susceptible area had faster MD deterioration (dB/year) than those in the less susceptible area within four years (- 0.32 ± 0.51 vs. - 0.05 ± 0.45, p = 0.047). A total of 16.9% of eyes, all in the susceptible area, had localized VF progression at DH corresponding area. CONCLUSION: Disc hemorrhage in the superotemporal and inferotemporal regions had more subsequent structural and functional deterioration compared with the eyes with DHs in the temporal quadrant and nasal area.

Migraine and increased risk of developing open angle glaucoma: a population-based cohort study.

BACKGROUND: Migraine is linked to endothelial dysfunction and is considered to be a systemic vasculopathy. Interestingly, systemic vascular diseases also occur in glaucoma patients and are considered to be vascular risk factors. Whether migraine is simply a concomitant condition in glaucoma patients or a risk factor per se for glaucoma remains unknown. Thus, in the present study, we investigated the risk for open angle glaucoma (OAG) in migraineurs using a 10-year follow-up study that employed a nationwide population-based dataset in Taiwan. METHODS: This retrospective matched-cohort study used data sourced from the Longitudinal Health Insurance Database 2000. We included 17,283 subjects with migraine in the study cohort and randomly selected 69,132 subjects from the database for the comparison group. Each subject in this study was individually traced for a 10-year period to identify those subjects who subsequently received a diagnosis of OAG. The age-adjusted Charlson's comorbidity index (ACCI) score was utilized to compute the burden of comorbidity in each subject. Multivariate regression analysis was used to assess risk factors for OAG in migraineurs. Cox proportional hazards regression was performed to compare the 10-year risk of OAG between the migraineurs and the comparison cohort. RESULTS: Migraineurs had more vascular comorbidities than the comparison cohort. The overall incidence of OAG (per 1000 person-years) was 1.29 and 1.02, respectively, for migraineurs and the comparison cohort during the 10-year follow-up period. Age, hyperlipidemia, and diabetes mellitus were three significant risk factors for OAG in migraineurs. After adjusting for patients' age and vascular comorbidities, migraineurs were found to have a 1.68-fold (95% confidence interval [CI], 1.20-2.36) greater risk of developing OAG than the comparison cohort, in subjects with an ACCI score of 0. This association became statistically nonsignificant in subjects with ACCI scores of 1-2 or ≥ 3. CONCLUSION: Migraine is associated with a higher risk of OAG for patients with no comorbidity who are aged under 50 years.

Incidence and risk of attention-deficit hyperactivity disorder in children with amblyopia: A nationwide cohort study.

IMPORTANCE: The association between visual deficits and attention disorders has been reported but remains unproven. BACKGROUND: The objective of this study was to evaluate the risk of attention-deficit hyperactivity disorder (ADHD) in children with amblyopia. DESIGN: Population-based, cohort study. PARTICIPANTS: The dataset from the Taiwan National Health Insurance Research Database in 2000 to 2010. METHODS: A total of 6817 patients aged <18 years with newly diagnosed amblyopia were identified. Four age- and sex-matched controls without amblyopia were included for each patient, that is, 27268 controls. MAIN OUTCOME MEASURES: The primary outcome was the risk of ADHD. The secondary outcomes were age at ADHD onset and use of ADHD medication. RESULTS: During a mean observation period of 7.18 years, the incidence of ADHD per 1000 person-years was 7.02 in the amblyopia group and 4.61 in the control group (P < 0.0001). The ADHD risk in the amblyopia group was 1.81 times that in the control group (hazard ratio 1.81; 95% confidence interval 1.59-2.06). After stratification by amblyopia subtype, the greatest risk was in the deprivation type (hazard ratio 2.14; 95% confidence interval 1.56-2.92) followed by the strabismic (hazard ratio 2.09; 95% confidence interval 1.15-3.79) and refractive (hazard ratio 1.76; 95% confidence interval 1.54-2.02) types. Age at ADHD onset was younger in the amblyopia group (median 8.14 vs 8.45 years; P = 0.0096). The average duration of neuropsychiatric medication use was comparable between groups (P = 0.98). CONCLUSIONS AND RELEVANCE: The ADHD risk is higher in children with amblyopia.

Long-term follow-up of retinal nerve fiber layer cleavages in glaucoma patients and suspects.

PURPOSE: To investigate the structural and functional characteristics and change of the retinal nerve fiber layer cleavages (RNFLCs) in glaucoma patients and suspects in long-term follow-up. METHODS: This is a retrospective longitudinal study. Within 43 eyes of 30 subjects, 62 RNFLC locations were detected on color fundus photography. Basic ophthalmic examinations, color fundus photography, optical coherence tomography (OCT), and visual field (VF) test were performed in 6-month intervals. Clinical characteristics and the structural and functional changes of the cleaved areas were analyzed. RESULTS: RNFLC and localized vitreoretinal traction occurred most commonly along the superotemporal retinal vessel arcade. Nine locations had corresponding defects on OCT deviation map, while 31 locations were associated with defects on OCT deviation map. Three locations had corresponding VF defects. More of the non-highly myopic eyes had lamellar hole than the highly myopes (p = 0.038). The RNFLC lesions in glaucomatous eyes were more frequently associated with OCT defects on deviation map (p = 0.021). There was no difference in the presence of lamellar hole or the number of RNFLCs between the glaucomatous and non-glaucomatous eyes. During a 66.8 ± 37.8-month follow-up, there was no structural or functional progression of the RNFLCs as determined by color fundus photography, VF test, and GPA of OCT interpreted by three ophthalmologists. There was no statistically significant change of RNFLC area (p = 0.268). CONCLUSIONS: RNFLC did not show detectable functional or structural change in early glaucoma patients and suspects after long-term follow-up.

Inhibition of matrix metalloproteinase activity reverses corneal endothelial-mesenchymal transition.

Ex vivo culture or regeneration of corneal endothelial cells often is subjected to gradual endothelial-mesenchymal transition and loss of function. Here, we found that during ex vivo culture, bovine corneal endothelial cells underwent endothelial-mesenchymal transition and had an up-regulated expression and activity of matrix metalloproteinases. Inhibition of matrix metalloproteinase activity in confluent bovine corneal endothelial cells decreased the level of endothelial-mesenchymal transition regulators: snail and slug. The phosphorylation and degradation of the key Wnt signaling pathway modulator active ß-catenin also were accelerated with the broad-spectrum matrix metalloproteinase inhibitor Marimastat, which may result from decreased N-cadherin shedding and increased intact N-cadherin molecules on the cell membrane. Intracameral injection of Marimastat also suppressed basic fibroblast growth factor-induced endothelial-mesenchymal transition in a rat corneal endothelium cryo-injury model and significantly diminished the corneal edema. Our study indicated that inhibition of matrix metalloproteinase activity can reverse endothelial-mesenchymal transition and preserve the function of corneal endothelial cells both during ex vivo culture and in vivo. This may offer a potential therapeutic target in regenerative medicine for the treatment of corneal endothelial dysfunctions.

Phenotypes of trypsin- and collagenase-prepared bovine corneal endothelial cells in the presence of a selective Rho kinase inhibitor, Y-27632.

PURPOSE: To optimize isolation of viable bovine corneal endothelial cells (BCECs), we evaluated the effectiveness of various preparation protocols. This entailed comparing the effects of collagenase A and trypsin in the presence and absence of a Rho kinase inhibitor, Y-27632, on proliferation and tight junctional and cytoskeletal integrity during their expansion. METHODS: 5-bromo-2'-deoxyuridine (BrdU) incorporation evaluated cell proliferation. Western blot analysis evaluated F-actin, zonule occludin, and ZO-1 associated nucleic acid binding protein (ZONAB) and RhoA expression. Rho A pulldown assay evaluated Rho A activity. RESULTS: In the trypsin (TrypLE)-prepared BCECs, BrdU incorporation decreased whereas nuclear ZONAB expression increased and became stable from day 3 to 7. In contrast, in the collagenase-A-prepared BCECs, we observed preserved ZO-1 integrity, invariant nuclear ZONAB expression, and dense cortical F-actin expression, and BrdU incorporation was invariant from days 1 to 7. Y-27632 did not increase BrdU incorporation and nuclear ZONAB expression in the TrypLE-prepared and the collagenase-A-prepared BCECs. Moreover, Y-27632 increased irregular cellular morphology and downregulated the expression of ZO-1 in the collagenase-A-prepared BCECs from days 1 to 7. Y-27632 inhibited RhoA activation irrespective of whether the cells were isolated with trypsin or collagenase A. CONCLUSIONS: It is preferable to isolate BCECs with collagenase A and expand them without Y-27632. With this protocol, proliferative activity and tight junctional and cytoskeletal integrity are better preserved than if trypsin is used in the presence or absence of Y-27632.

Risk factors for depressive symptoms in glaucoma patients: a nationwide case-control study.

PURPOSE: The purpose was to investigate the risk factors for depressive symptoms in glaucoma patients. METHODS: From the Longitudinal Health Insurance Database in Taiwan, we included 1190 glaucoma patients with subsequent depression diagnoses in the case group and randomly selected 4673 glaucoma patients without depression diagnoses as the control group, matched by age, sex, and time of glaucoma diagnosis. The age-adjusted Charlson comorbidity index (ACCI) score was used to compute the burden of comorbidity for each patient. Current use (past 6 months) of topical antiglaucoma medications and systemic medications was identified. Multivariate regression was used to analyze the risk factors for depression. RESULTS: The mean age for glaucoma patients was 61.88 years. Patients with depressive symptoms had significantly higher ACCI scores (P < .0001). The current use of any topical antiglaucoma medications was not associated with an increased risk for depression. However, higher ACCI scores (P < .0001), cerebrovascular diseases (odds ratio [OR] = 1.324, 95 % confidence interval [CI] = 1.118--1.568), dementia (OR = 2.647, 95 % CI = 2.142-3.270), thyroid diseases (OR = 1.720, 95 % CI = 1.366-2.165), headaches (OR = 1.299, 95 % CI = 1.112-1.518), and current use of systemic ß-blockers (OR = 1.782, 95 % CI = 1.538-2.065) and calcium channel blockers (OR = 1.396, 95 % CI, 1.197-1.629) were found to increase the risk of depression in glaucoma patients. CONCLUSIONS: In this study, a comorbidity burden was a significant risk factor for depression in glaucoma patients, particularly for those currently using systemic ß-blockers and calcium channel blockers.

Macular tractional retinoschisis in proliferative diabetic retinopathy: clinical characteristics and surgical outcome.

PURPOSE: To evaluate the clinical characteristics and surgical outcome of macular tractional retinoschisis (TRS) as compared with tractional retinal detachment (TRD) in proliferative diabetic retinopathy (PDR). METHODS: This retrospective, longitudinal study collected consecutive cases with optical coherence tomography (OCT)-confirmed TRS and TRD between January 2007 and June 2013. All cases had surgical treatment. Their preoperative findings and follow-up data were subsequently compared. RESULTS: Thirty-two eyes (32 patients) with TRS and 32 eyes (32 patients) with TRD were included. The TRS group had more clinically inactive fibrosis and less extensive fibrovascular proliferation than the TRD group. The involved area and height of the schisis varied among cases; associated macular abnormalities included inner macular cyst (43.75%), lamellar hole (12.5%) and foveal detachment (9.38%); sequential OCT in some cases showed a progression of macular changes. Both groups had significant visual improvement after surgery. Of the patients with TRS, 40.62% had residual retinoschisis. Preoperative best-corrected visual acuity (BCVA), postoperative BCVA and improvement in visual acuity showed no significant difference between TRS and TRD. CONCLUSIONS: Unique features exist for macular TRS in PDR. Visual function may benefit from vitreous surgery despite residual macular abnormalities in some cases.

The impact of visual function on staircase use performance in glaucoma.

OBJECTIVES: This cross-sectional study aimed to investigate the relationship between visual function and staircase use in glaucoma. METHODS: Overall, 181 patients with glaucoma with a best-corrected visual acuity ≥20/400 were classified into mild to moderate (mean deviation [MD] ≥ -12 dB) and advanced (MD < -12 dB) groups, according to 24-2 VF of the worse eye. Staircase use evaluation included stair descent and ascent time (SDT/SAT) and self-reported stair difficulty. Correlations between staircase use and visual function were analysed, including binocular visual acuity, integrated visual field (IVF), and binocular contrast sensitivity (CS). Linear and logistic regression adjusted by age, sex, and comorbidities inspected the effect of visual parameters on SDT/ SAT and stair difficulty. RESULTS: Visual function best correlated with SDT among staircase use. In mild to moderate glaucoma, area under the log CS function (AULCSF) (ß = -1.648, P = 0.031) was the only visual factor significant for SDT (adjusted R2 = 0.106), whereas AULCSF (ß = -1.641, P = 0.048) and MD of IVFINF0-24 (ß = -0.089, P = 0.013) were associated with SDT in advanced glaucoma (adjusted R2 = 0.589). The AULCSF was the only significant visual parameter related to SAT (ß = -1.125, P = 0.019) and stair difficulty (adjusted odds ratio = 0.003; 95% confidence interval, 0-0.302; P = 0.013). CONCLUSIONS: SDT provides a higher correlation with visual function than self-reported stair difficulty. Patients with impaired CS or inferior IVF defects should be advised on stair safety and referred to low-vision services.

Topical ganciclovir treatment in patients with cytomegalovirus endotheliitis receiving penetrating keratoplasty.

BACKGROUND: To report seven cases diagnosed as cytomegalovirus endotheliitis and treated with topical 2% ganciclovir following penetrating keratoplasty. DESIGN: A retrospectively comparative case series. PARTICIPANTS: A retrospective interventional case series, including seven eyes of seven patients with cytomegalovirus endotheliitis after penetrating keratoplasty. METHODS: Clinical and immunological characteristics were studied in seven penetrating keratoplasty cases with positive quantitative polymerase chain reaction results for cytomegalovirus DNA from aqueous taps and treated with topical 2% ganciclovir. MAIN OUTCOME MEASURES: Clinical features and responses to topical 2% ganciclovir. RESULTS: Seven immunocompetent patients experienced acute anterior inflammation with graft oedema and pigmented keratic precipitates after penetrating keratoplasty. Their immunological profiles showed immunoglobulin G cytomegalovirus (+) and immunoglobulin M cytomegalovirus (-) in all cases. Topical 2% ganciclovir was prescribed every 2 to 3 h daily as induction therapy and every 4 h as long-term maintenance therapy. All cases had undetectable cytomegalovirus DNA after follow-up aqueous taps. Topical 2% ganciclovir preserved endothelium of cytomegalovirus-infected grafts at early stage and also provided a steady anticytomegalovirus environment for further regrafting in failed grafts at late stage. Acute inflammation reactivated in two cases and was suppressible by steroid under topical ganciclovir. No delayed re-epithelialization and any toxicity were observed. To date, no case treated in this way had displayed cytomegalovirus recurrence. CONCLUSIONS: Continuous topical 2% ganciclovir and a topical steroid adjusted by anterior inflammation are suggested after penetrating keratoplasty in all cases with cytomegalovirus endotheliitis to prevent cytomegalovirus recurrence.

Relationship between the Macular Microvasculature and Central Visual Field Sensitivity in Patients with Advanced Glaucoma.

PURPOSE: To evaluate the relationship between central visual field sensitivity (cVFS) and the structural parameters in patients with advanced glaucoma. DESIGN: Cross-sectional study. METHODS: In total, 226 eyes of 226 patients with advanced glaucoma were classified into the "minor central defect" (mean deviation on 10-2 visual field test [MD10] > -10 dB) and "significant central defect" (MD10 ≤ -10 dB) groups. We examined the structural parameters using RTVue OCT and angiography, including the retinal nerve fiber layer, ganglion cell complex, peripapillary vessel density (VD), and superficial and deep macular VD (mVD). The assessment of cVFS included MD10 and the mean deviation of the central 16 points on the 10-2 VF test (MD16). We used Pearson correlation and segmented regression to assess the global and regional relationships between the structural parameters and cVFS. MAIN OUTCOME MEASURES: Correlation between structural parameters and cVFS. RESULTS: In the minor central defect group, the best global correlations existed between the superficial macular and parafoveal mVD and MD16 (r = 0.52 and 0.54, P < 0.001). In the significant central defect group, superficial mVD best correlated with MD10 (r = 0.47, P < 0.001). Segmented regression between superficial mVD and cVFS revealed no breakpoint was found as MD10 declined, but a breakpoint was identified at -5.95 dB for MD16, which was statistically significant (P < 0.001). The regional correlations between the grid VD and sectors of the central 16 points were significant (r = 0.20-0.53, P= 0.010 ∼P < 0.001). CONCLUSIONS: The fair global and regional relationships between mVD and cVFS suggest that mVD may be beneficial for monitoring cVFS in patients with advanced glaucoma. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Autophagy deficiency protects against ocular hypertension and neurodegeneration in experimental and spontanous glaucoma mouse models.

Glaucoma is a group of diseases that leads to chronic degeneration of retinal ganglion cell (RGC) axons and progressive loss of RGCs, resulting in vision loss. While aging and elevated intraocular pressure (IOP) have been identified as the main contributing factors to glaucoma, the molecular mechanisms and signaling pathways triggering RGC death and axonal degeneration are not fully understood. Previous studies in our laboratory found that overactivation of autophagy in DBA/2J::GFP-LC3 mice led to RGC death and optic nerve degeneration with glaucomatous IOP elevation. We found similar findings in aging GFP-LC3 mice subjected to chronic IOP elevation. Here, we further investigated the impact of autophagy deficiency on autophagy-deficient DBA/2J-Atg4bko and DBA/2J-Atg4b+/- mice, generated in our laboratory via CRISPR/Cas9 technology; as well as in Atg4bko mice subjected to the experimental TGFß2 chronic ocular hypertensive model. Our data shows that, in contrast to DBA/2J and DBA/2J-Atg4b+/- littermates, DBA/2J-Atg4bko mice do not develop glaucomatous IOP elevation. Atg4b deficiency also protected against glaucomatous IOP elevation in the experimental TGFß2 chronic ocular hypertensive model. Atg4 deletion did not compromise RGC or optic nerve survival in Atg4bko mice. Moreover, our results indicate a protective role of autophagy deficiency against RGC death and ON atrophy in the hypertensive DBA/2J-Atg4b+/- mice. Together, our data suggests a pathogenic role of autophagy activation in ocular hypertension and glaucoma.