Predicting Lifetime Transition Risk of Severe Visual Field Defects Using Monte Carlo Simulation in Japanese Patients with Primary Open-Angle Glaucoma.

PURPOSE: To maintain visual fields and quality of life over a lifetime, medical practice must be conducted taking into consideration not only visual field progression but also future visual field changes that occur over the patients' expected lifespan. The purpose of this study is to investigate the feasibility of establishing a model that predicts prognosis, estimating the proportion of glaucoma patients with severe visual field defects. PATIENTS AND METHODS: The data of 191 patients with primary open-angle glaucoma, with a predominance of normal-tension glaucoma, were used for this study. The model was developed based on patients' backgrounds and risk factors, using Monte Carlo simulation. A "severe visual field defect" was defined as ≤-20 dB. The mean deviation (MD) value for 10,000 virtual patients in each simulation pattern (144 patterns) was calculated using a predictive formula to estimate the MD slope, and the effects of risk factors and intraocular pressure (IOP) reduction on the proportion of patients with severe visual field defects were evaluated. RESULTS: Younger age, later-stage disease, more severe glaucomatous structural abnormalities and the presence of disc hemorrhage were associated with an increase in the progression rate of patients with severe visual field defects. Conversely, lower IOP was associated with a decrease in this rate. CONCLUSION: Combining regression analysis with Monte Carlo simulation could be a useful method for developing predictive models of prognosis in glaucoma patients.

Ocular hypotensive effects of prostaglandin analogs in Japanese patients with normal-tension glaucoma: a literature review.

PURPOSE: This paper aimed to evaluate the intraocular pressure (IOP)-lowering effects of prostaglandin analogs (PGAs) in Japanese patients with normal-tension glaucoma (NTG) by reviewing the current literature. METHODS: In February 2018, database searches were performed in PubMed, Embase, ProQuest, and the Japanese databases JAPICDOC and JMEDPlus. Studies were sorted into two categories: Category 1 consisted of studies of patients with NTG who reported reduced IOP values and Category 2 consisted of studies of patients with NTG who had IOP values at predosing and a final evaluation point. Search terms included ([unoprostone or latanoprost or travoprost or bimatoprost or tafluprost] and [glaucoma] and [Japan or Japanese]). The weighted ocular hypotensive efficacy was calculated. A scatter plot analysis was performed and a regression equation was calculated for each medication. The fitting of each regression equation was evaluated by the least squares method. RESULTS: Eleven articles were eligible for Category 1 and 25 articles for Category 2. In the rank order of IOP-lowering efficacy of PGAs, bimatoprost was the strongest and latanoprost the weakest. Travoprost and tafluprost had almost the same level of ocular hypotensive effect, and both were stronger than latanoprost. The scatter plot analysis showed that all PGAs reduced IOP by 15%-20%. At higher IOP (17-18 mmHg), the ocular hypotensive effect was almost the same with latanoprost, travoprost, and tafluprost. In contrast, at lower IOP (12-15 mmHg), the IOP reduction with latanoprost was weaker than with travoprost or tafluprost. CONCLUSION: This literature review of the ocular hypotensive effects of PGAs in Japanese patients with NTG highlighted that PGAs had different ocular hypotensive effects. Ophthalmologists should understand the IOP-lowering profiles of various PGAs and apply them to patients with NTG on a case-by-case basis. TRIAL REGISTRATION: UMIN Clinical Trials Registry UMIN000032344.

Effect of quantitative intraocular pressure reduction on visual field defect progression in normal tension glaucoma under medical therapy applying Markov model.

PURPOSE: To quantitatively evaluate the association of intraocular pressure (IOP) reduction with visual field defect (VFD) progression in normal tension glaucoma (NTG) under medical therapy. PATIENTS AND METHODS: Clinical data for 622 eyes of 311 primary open-angle glaucoma and NTG patients were collected from April 2006 to March 2016. Of these patients, those with normal IOP, glaucomatous VFD by Anderson's criteria, corrected visual acuity ≥0.7, >5 years of medical therapy, ≥5 visual field tests at least five times at 12-month intervals, visual field testing reliability coefficients of ≤33%, and mean deviation (MD) exceeding below -20 dB in the initial visual field test were included in this retrospective data analysis. MD and IOP data were collected at baseline and after 5 years. Following MD categorization into stages I to IV, stage transition matrices were generated using a Markov model to evaluate VFD changes. Eyes were divided based on IOP reduction (0%, 10%, 15%, 20%, 25%, 30%) from baseline. VFD aggravations were compared using the Markov model and MD slopes with IOP reduction rates as cutoff values. RESULTS: Overall, 132 eyes of 132 NTG patients fulfilled the eligibility criteria. MD decreased significantly (P<0.0001) at 5 years vs baseline. During follow-up, visual field stage using the Markov model was constant in ~60%, with transitions in ~40%. IOP decreased significantly (P>0.001) at 5 years vs baseline. Though MD slopes did not differ significantly between each of the groups that achieved the various IOP reduction cut-off values and the corresponding group that did not achieve the cut-off values, a significant difference (P=0.0432) in VFD was found between the group that achieved the 25% cut-off value and the group that did not when evaluated using the Markov model. CONCLUSION: In NTG patients, VFD aggravation was significantly suppressed in groups with IOP reductions of ≥25% from baseline.

Long-term progression of visual field defects and related factors in medically treated normal tension glaucoma.

PURPOSE: To analyze factors related to long-term progression of visual field defects (VFD) in patients with normal tension glaucoma (NTG) under medical therapy. PATIENTS AND METHODS: Clinical data from 622 eyes of 311 primary open-angle glaucoma and NTG patients were collected from April 2006 to March 2016. Of these patients, those with normal intraocular pressure (IOP); glaucomatous VFD judged by Anderson's criteria; corrected visual acuity ≥0.7; receiving more than 6 years medical therapy; having undergone ≥10 visual field tests performed at 6-month intervals using a Humphrey field analyzer (Swedish Interactive Threshold Algorithms standard, C 24-2 program); and having reliability coefficients of visual field testing <33% and mean deviation (MD) more than -20 decibels in the initial visual field test were included in data analysis. The relationship between MD slope deterioration at final observation and consecutive decreases in MD value during the observation period, as well as clinical characteristics and IOP-related factors, were analyzed. RESULTS: Of 134 eyes in 134 NTG patients meeting all eligibility criteria, significant MD slope deterioration was observed in 80 eyes (59.7%). MD slope deterioration was significantly associated with consecutive decreases in MD values (Cochran-Armitage trend test: P=0.0000; univariate logistic regression analysis: P<0.0001). While no significant relationship was observed between central corneal thickness, refractive error, or prevalence of disc hemorrhage, consecutive decreases in MD value was significantly related to MD slope deterioration (univariate logistic regression analysis: P<0.0001). A reduction of IOP during the follow-up period was significantly related to nondeterioration of the MD slope (multivariate logistic regression analysis: P=0.0020). CONCLUSION: In this 6-year observation of NTG patients treated with medical therapy, the occurrence of three or more consecutive decreases in MD value was significantly associated with visual field deterioration. Reduction in IOP was postulated to be contributing in the prevention of VFD progression.

Prediction of Visual Field Progression in Patients with Primary Open-Angle Glaucoma, Mainly Including Normal Tension Glaucoma.

An objective method to predict individual visual field progression will contribute to realise personalised medication. The purpose of this study was to establish a predictive formula for glaucomatous visual field progression in patients with Primary open-angle glaucoma, mainly including normal tension glaucoma. This study was a large-scale, longitudinal and retrospective study including 498 eyes of 312 patients visiting from June 2009 to May 2015. In this analysis, 191 eyes of 191 patients meeting all eligible criteria were used. A predictive formula to calculate the rate of glaucomatous visual field progression (mean deviation slope) was obtained through multivariate linear regression analysis by adopting "Angle of Retinal Nerve Fibre Layer Defect" at the baseline, "Vertical Cup-Disc ratio" at the baseline, "Presence or absence of Disc Haemorrhage" during the follow-up period, and "Mean IOP change (%)" during the follow-up period as predictors. Coefficient of determination of the formula was 0.20. The discriminative ability of the formula was evaluated as moderate performance using receiver operating characteristic analysis, and the area under the curve was approximately 0.75 at all cut-off values. Internal validity was confirmed by bootstrapping. The predictive formula established by this type of approach might be useful for personalised medication.