Koji Nitta

Does the enlargement of retinal nerve fiber layer defects relate to disc hemorrhage or progressive visual field loss in normal-tension glaucoma?

PurposeWe investigated the difference in clinical characteristics between cases with enlarged retinal nerve fiber layer defects (RNFLD) and stable RNFLDs in normal-tension glaucoma (NTG). Patients and MethodsWe retrospectively reviewed NTG patients that were diagnosed and followed up for at least 3 years at 1-month to 2-month intervals by the same examiner, and selected eyes with distinct RNFLD borders. Using fundus photographs, for which we extracted only a blue ingredient and processed it into black and white, we measured RNFLD angles and divided NTG cases into 2 groups, enlarged RNFLD and stable RNFLD, and compared the clinical characteristics between both groups. ResultsNinety-three eyes from 93 patients (mean follow-up, 8.2 y) were selected and enlargement of RNFLD was detected in 55 eyes. Disc hemorrhage (DH) was found in 35 of 55 eyes (63.6%) in the enlarged group and in 6 of 38 eyes (15.8%) in the stable group (P<0.0001). Twenty-one eyes (38.2%) from the enlarged group exhibited recurrent DH. In 48 eyes (87.3%) from the enlarged group, the enlargement of RNFLD was toward the fovea. When DHs located apart from RNFLD were excluded, RNFLD enlarged in the direction of DH in 21 of 25 eyes (84.0%). The cumulative probability of non progression in the visual field was significantly lower in the enlarged group (10–year survival rate: 0.52±0.11) than in the stable group (10-year survival rate: 0.89±0.08) (P=0.0019). ConclusionsThe enlargement of RNFLD in NTG was closely associated with DH occurrence and the deterioration of visual field.

Clinical Significance of Owl Eye Morphologic Features by In Vivo Laser Confocal Microscopy in Patients With Cytomegalovirus Corneal Endotheliitis

OBJECTIVE To demonstrate the clinical significance of owl eye morphologic features observed by in vivo laser confocal microscopy in patients with cytomegalovirus (CMV) corneal endotheliitis. DESIGN Observational case series. METHODS participants: Six eyes of 6 patients (6 men; mean age, 73.3 years) with cytomegalovirus corneal endotheliitis diagnosed by clinical manifestations together with polymerase chain reaction from aqueous humor samples. intervention: All patients were examined by slit-lamp biomicroscopy and in vivo laser confocal microscopy. main outcome measures: Clinical manifestations were summarized by reviewing medical records. Selected confocal images of corneal layers were evaluated qualitatively for shape and degree of light reflection of abnormal cells and deposits. RESULTS All patients had long histories of anterior uveitis with intraocular pressure elevation, corneal edema with keratic precipitates, and decrease of endothelial cell densities. Coin-shaped lesions were observed by slit lamp only in 1 patient at the first visit and in 2 additional patients at subsequent follow-up. In all patients, confocal microscopy demonstrated reduced subepithelial nerves, subepithelial opacity, increased reflectivity of keratocytes, highly reflective dots, and needle-shaped bodies. Owl eye morphologic features were observed consistently in all patients at the initial visit, and highly reflective round bodies were detected in 5 patients; most notably, these confocal features were reversible after resolution of endotheliitis. CONCLUSIONS Owl eye morphologic features and highly reflective round bodies observed by confocal microscopy may be useful as an adjunct for the noninvasive diagnosis of cytomegalovirus corneal endotheliitis. Reversibility of these features after resolution of endotheliitis may be useful for monitoring the therapeutic effects without multiple anterior chamber tap.

Influence of clinical factors on blue-on-yellow perimetry for diabetic patients without retinopathy: comparison with white-on-white perimetry.

Purpose: To investigate the influence of clinical factors (duration of diabetes mellitus, fasting blood sugar level, fructosamine concentration, and hemoglobin A1c) on blue-on-yellow (B-on-Y) perimetry compared with white-on-white (W-on-W) perimetry for diabetics without retinopathy. Methods: Both B-on-Y perimetry and W-on-W perimetry were performed for 33 diabetics without retinopathy. Thirty-three subjects with healthy eyes served as age-matched controls. Results: For both diabetic patients and controls, mean deviation (MD) and corrected pattern SD of perimetry showed no difference irrespective of B-on-Y or W-on-W perimetry. For diabetics, MD of B-on-Y perimetry decreased in proportion to the morbid period with diabetes mellitus, with the same being true with deterioration of the clinical factors. Multiple regression analysis disclosed no differences in MD of clinical factors for W-on-W perimetry, despite the duration of diabetes mellitus exerting a significant influence on MD of B-on-Y perimetry. Conclusion: Even at the premorbid stage of diabetic retinopathy, longer duration of diabetes mellitus and longer persistence of poorly controlled diabetes mellitus are associated with an insidious progress of dysfunction in the retinal blue cone system.

Stereoscopic Analysis of Optic Nerve Head Parameters in Primary Open Angle Glaucoma: The Glaucoma Stereo Analysis Study

Purpose The Glaucoma Stereo Analysis Study (GSAS), a cross sectional multicenter collaborative study, used a stereo fundus camera to assess various morphological parameters of the optic nerve head (ONH) in glaucoma patients and investigated the relationships between these parameters and patient characteristics. Subjects and Methods The study included 187 eyes of 187 subjects with primary open angle glaucoma or normal tension glaucoma (male: female  = 100: 87, age  = 61±9 years). Stereo pairs of ONH photographs were made with a stereo fundus camera (nonmyd WX). ONH morphological parameters were calculated with prototype analysis software. In addition to 35 standard parameters, we defined three novel parameters: disc tilt angle, rim decentering, and the absolute value of rim decentering. The correlation between each parameter and patient characteristics was analyzed with Spearmans rank correlation coefficient. Results Patient characteristics included refractive error of −3.38±3.75 diopters, intraocular pressure (IOP) of 13.6±2.6 mmHg, and visual field mean deviation (MD) of −4.71±3.26 dB. Representative ONH parameters included a horizontal disc width of 1.66±0.28 mm, vertical disc width of 1.86±0.23 mm, disc area of 2.42±0.63 mm2, cup area of 1.45±0.57 mm2, and cup volume of 0.31±0.22 mm3. Correlation analysis revealed significant negative associations between vertical cup-to-disc ratio (0.82±0.08) and MD (r = −0.40, P<0.01) and between disc tilt angle (10.5±12.5 degrees) and refractive error (r = −0.36, P<0.01). Seventy-five percent of the eyes had a positive value for rim decentering (0.30±0.42), indicating that rim thinning manifested more often as an inferior lesion than a superior lesion. Conclusion We used stereoscopic analysis to establish a database of ONH parameters, which may facilitate future studies of glaucomatous changes in ONH morphology.

Differentiation of glaucomatous optic discs with different appearances using optic disc topography parameters: The Glaucoma Stereo Analysis Study

The Glaucoma Stereo Analysis Study (GSAS) is a multicenter collaborative study of the characteristics of glaucomatous optic disc morphology using a stereo fundus camera. Using GSAS dataset, the formulas for predicting different glaucomatous optic disc appearances were established. The GSAS dataset containing three-dimensionally-analyzed optic disc topographic parameters from 187 eyes with primary open-angle glaucoma was assessed with discrimination analyses to obtain formulas predictive of glaucomatous optic disc appearances: focal ischemic (FI); generalized enlargement (GE), myopic glaucomatous (MY), and senile sclerotic (SS). Using 38 optic disc parameters-substituted discrimination analyses with a stepwise forward-selection method, six parameters (temporal and nasal rim-disc ratios, mean cup depth, height variation contour, disc tilt angle, and rim decentering absolute) were selected into the formulas. The area under the receiver operating characteristic curves for predicting the four disc types with established formulas were 0.88, 0.91, 0.93, and 0.86 for FI, MY, SS, and GE, respectively. Age, visual acuity, refractive error, glaucoma (normal or high-tension glaucoma), and baseline intraocular pressure differed significantly among the four optic disc types, suggesting the appearances represent different clinical glaucoma phenotypes. Using six optic disc topographic parameters obtained by stereo fundus camera, the GSAS classification formulas predicted and quantified each component of different optic disc appearances in each eye and provided a novel parameter to describe glaucomatous optic disc characteristics.

Estimation of the Disc Damage Likelihood Scale in primary open-angle glaucoma: the Glaucoma Stereo Analysis Study

PurposeThe Glaucoma Stereo Analysis Study (GSAS), a cross-sectional multicenter collaborative study, used a stereo fundus camera (nonmyd WX) to assess various morphological parameters of the optic nerve head (ONH) in glaucoma patients. We examined the associations between the Disc Damage Likelihood Scale (DDLS), a grading system for estimating glaucomatous ONH damage, and each parameter.MethodsThe study included 187 eyes of 187 patients with primary open-angle glaucoma or normal-tension glaucoma. ONH morphological parameters including the DDLS stage were calculated with prototype analysis software. Three independent graders classified each optic disc appearance into four different types: focal ischemic, myopic glaucomatous, senile sclerotic, and generalized enlargement. The correlations between the DDLS and patient characteristics or each ONH parameter were analyzed with Spearman’s rank correlation coefficient.ResultsThe DDLS was correlated positively with baseline intraocular pressure and visual field pattern standard deviation, and negatively with visual field mean deviation. The DDLS was strongly correlated with vertical cup-to-disc ratio and horizontal cup-to-disc ratio positively, and with minimum rim-disc ratio negatively. The mean DDLS stage in the myopic glaucomatous type tended to be higher than the scores in other types.ConclusionThe DDLS obtained through three-dimensional ONH analysis correlates well with the severity of glaucomatous ONH and visual field damage.

Disc Hemorrhage is a Sign of Progression in Normal-tension Glaucoma

Therefore, considering the explanations, it may be more appropriate to consider disc hemorrhage as a sign of progression. If we assume disc hemorrhage as a sign of progression, risk factor for disc hemorrhage can be a risk factor for glaucoma progression. Prata et al5 performed a study in eyes with disc hemorrhage and found baseline VF mean deviation and older age to be significant risk factors for fast progression after disc hemorrhage. If we consider disc hemorrhage as an early sign of progression, the observation of RNFL defect widening after disc hemorrhage what we frequently encounter in clinical practice or Nitta et al’s1 recent report that disc hemorrhage was associated with both structural RNFL enlargement and functional VF progression seemed to be quite natural. Conclusively, after I read the paper by Nitta et al,1 which found the eyes with RNFL progression showed significantly higher probability of concurrent disc hemorrhage, I am more inclined to believe that disc hemorrhage is a sign of progression rather than risk factor for progression, and the strong association between disc hemorrhage and progression should be interpreted as such.

Is high myopia a risk factor for visual field progression or disk hemorrhage in primary open-angle glaucoma?

Purpose The purpose of this study was to clarify differences between highly myopic and non-myopic primary open-angle glaucoma (POAG) patients, including normal-tension glaucoma patients. Patients and methods A total of 269 POAG patients were divided into two groups: patients with ≥26.5 mm of axial length (highly myopic group) and patients with <24.0 mm of axial length (non-myopic group). Results We analyzed 53 highly myopic and 93 non-myopic POAG patients. Age at first visit of the highly myopic group was significantly less than that of the non-myopic group (P<0.0001). Baseline intraocular pressures (IOPs) showed no significant differences. Follow-up IOPs of the non-myopic group were significantly lower than those of the highly myopic group (P=0.0009). According to the mean deviation definition of progression, the cumulative probability of non-progression of visual field (VF) loss was significantly greater in the highly myopic group (10-year survival rate, 73.7%±6.8%) than in the non-myopic group (10-year survival rate, 46.3%±5.8%; log-rank test, P=0.0142). The occurrence of disk hemorrhage (DH) in the non-myopic group (1.60±3.04) was significantly greater than that in the highly myopic group (0.93±2.13, P=0.0311). The cumulative probability of DH was significantly lower in the highly myopic group (10-year survival rate, 26.4%±5.4%) than in the non-myopic group (10-year survival rate, 47.2%±6.6%, P=0.0413). Conclusion Highly myopic POAG is considered as a combination of myopic optic neuropathy and glaucomatous optic neuropathy (GON). If GON is predominant, it has frequent DH and more progressive VF loss. However, when the myopic optic neuropathy is predominant, it has less DH and less progressive VF loss.

Validation of formula-predicted glaucomatous optic disc appearances: the Glaucoma Stereo Analysis Study

The Glaucoma Stereo Analysis Study (GSAS) is a multicentre collaborative study of the characteristics of glaucomatous optic disc morphology using a stereo fundus camera. Using the GSAS dataset, we previously established a formula for predicting different appearances of glaucomatous optic discs, although the formula lacked validation in an independent dataset. In this study, the formula was validated in another testing dataset.

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.