Incidence of deepening of the upper eyelid sulcus in prostaglandin-associated periorbitopathy with a latanoprost ophthalmic solution.

PURPOSE: Among some local side effects of prostaglandin-associated periorbitopathy (PAP), deepening of the upper eyelid sulcus (DUES) is the most prominent clinical feature, and is one of the most significant adverse cosmetic events. Here, we prospectively investigated the incidence of DUES in Japanese open-angle glaucoma patients initially treated with latanoprost (Xalatan 0.005%) ophthalmic solution. METHODS: This was an open-label prospective study. Facial photographs and subjective reports of the recognition of DUES were obtained at the beginning of latanoprost treatment and at 2, 4, and 6 months thereafter. Intraocular pressure (IOP) was measured at three consecutive visits before and after treatment with latanoprost. The incidence of DUES was evaluated objectively by three blinded investigators who compared the series of photographs. RESULTS: A total of 52 eyes of 52 newly diagnosed open-angle glaucoma Japanese patients (28 males, 24 females) were evaluated. The objective rate of DUES was 1/52 (2%; 95% CI 0.05 to 10.7%) at 2 months, 2/52 (4%; 95% CI 0.5 to 13.9%) at 4 months, and 3/52 (6%; 95% CI 1.2 to 16.9%) at 6 months. During this period, no patient self-reported an occurrence of DUES. Mean IOPs before and after treatment were 16.5±2.9 and 13.8±3.0 mm Hg, respectively. Latanoprost reduced the IOP significantly (P<0.0001, paired t-test). CONCLUSIONS: Latanoprost caused DUES rarely and had a robust IOP-lowering effect in Japanese glaucoma patients.

Initial trabeculectomy with mitomycin C in eyes with uveitic glaucoma with inactive uveitis.

PURPOSE: To analyse clinical outcomes of trabeculectomy with mitomycin C (MMC) in eyes with uveitic glaucoma (UG) with inactive uveitis and compare them to those in eyes with primary open-angle glaucoma (POAG). DESIGN: Retrospective non-randomized comparative interventional case series. METHODS: A total of 53 eyes with UG and 80 eyes with POAG that received MMC trabeculectomy as an initial ocular surgery with average follow-up of 5.4 years were reviewed retrospectively. The intraocular pressure (IOP) control and persistence of filtering bleb were analysed using the Kaplan-Meier life-table method based on two definitions of successful IOP control, ie complete success (IOP

Long-term follow-up of initial 5-fluorouracil trabeculectomy in primary open-angle glaucoma in Japanese patients.

PURPOSE: To evaluate the long-term efficacy and safety of initial trabeculectomy with subconjunctival 5-fluorouracil in Japanese patients with primary open-angle glaucoma. SUBJECTS AND METHODS: Clinical records of 117 eyes from 117 patients with records of up to 14 years were retrospectively analyzed using the appropriate statistical methods. RESULTS: The mean follow-up period was 6.2 +/- 3.6 years. Criteria for successful intraocular pressure control and success probability by Kaplan-Meier method at 12 years were intraocular pressure < 21 mm Hg without medication plus a 30% or more reduction in intraocular pressure, 50.4 +/- 5.2% (SE) 38.2 +/- 5.3%; and intraocular pressure < 16 mm Hg without medication plus a 30% or more reduction in intraocular pressure, 45.9 +/- 5.1% (36.5 +/- 5.2%). Cox multiple regression analysis showed that a younger age was associated with a higher success probability (P <0.01). Eyes with lower postoperative intraocular pressure tended to show more positive value of the MD slope (P = 0.0669), whereas 7% of successfully treated eyes showed a negative postoperative MD slope (P < 0.1). The probabilities for developing bleb leaks and bleb-related infections in eyes with a functioning bleb were 28.9 +/- 12.5% and 13.0 +/- 10.4% at 12 years. CONCLUSION: Trabeculectomy with 5-fluorouracil as an initial surgery in Japanese patients with primary open-angle glaucoma was effective for long-term control of glaucoma. However, the probability of late-onset bleb-related complications was not low in eyes with a functioning bleb, stressing the importance of constant care regarding bleb status.

Effects of latanoprost and unoprostone when used alone or in combination for open-angle glaucoma.

PURPOSE: To evaluate the effects of latanoprost and unoprostone on the intraocular pressure (IOP) and on the tonographic outflow facility in glaucoma patients when used alone or in combination. DESIGN: Open label randomized clinical study. METHODS: Fifty-two patients (52 eyes) with primary open-angle glaucoma were randomly divided into two groups. One group initially received only latanoprost 0.005% once daily and the other group, only unoprostone 0.12% twice daily. The study period was 12 weeks: in the first 6 weeks, latanoprost or unoprostone was given as monotherapy, and in the last 6 weeks, patients received both drugs. IOP was measured every 2 weeks by one investigator masked to the medication received by patients during the study period in the same hour as on the baseline day. At Weeks 0, 6, and 12, the coefficient of aqueous outflow was measured by tonography. RESULTS: With latanoprost monotherapy, the baseline IOP of 22.9 +/- 2.4 mm Hg (mean +/- SD) decreased to 16.9 +/- 2.1 mm Hg (P<.01). When unoprostone was added to latanoprost, the IOP remained at 16.7 +/- 2.5 mm Hg. With unoprostone monotherapy, the baseline IOP of 22.7 +/- 2.1 mm Hg decreased to 19.4 +/- 2.4 mm Hg (P<.01). When latanoprost was added to unoprostone, the IOP decreased to 16.8 +/- 1.7 mm Hg (P<.01). There was no significant change in the coefficient of aqueous outflow with monotherapy or the combined use of the drugs. CONCLUSIONS: The combination of latanoprost and unoprostone does not result in a more potent hypotensive effect than latanoprost alone.

[The ability of frequency doubling technology to detect abnormality of visual function in early glaucoma].

PURPOSE: To evaluate the ability of the Frequency Doubling Technology(FDT) threshold test in detecting abnormality of visual function in early glaucoma patients. SUBJECTS AND METHOD: The C-20 full threshold test of FDT was performed on 34 normal-tension glaucoma(NTG) patients and 39 primary open-angle glaucoma(POAG) patients with visual field defects limited to the upper or lower hemi-field as detected by Humphrey Field Analyzer(HFA) and on 79 normal control subjects. Optic disk findings and FDT results corresponding to the intact hemi-field were evaluated. FDT abnormalities in normal subjects were calculated as false positive rates in FDT. RESULT: The sensitivity and specificity of FDT, calculated based on optic disk findings, were 75.0% and 61.1% in POAG, and 61.1% and 66.7% in NTG, respectively, while the false positive rate in normal subjects was 11.4%. CONCLUSION: FDT can detect glaucomatous functional abnormality earlier than HFA.

[Usefulness of frequency doubling technology as a screening test for glaucoma].

PURPOSE: To evaluate the usefulness of frequency doubling technology (FDT) as a screening test. MATERIAL AND METHODS: One-hundred and six eyes of 106 patients with primary open-angle glaucoma and 66 eyes of 66 normal subjects were examined in a screening program using FDT. The test results were evaluated by comparison with the results obtained by Humphrey Field Analyzer (HFA) and/or the appearance of the optic disk. RESULTS: The sensitivity and specificity of FDT regarding the existence of abnormal points worse than mild relative loss were 88% and 95%, respectively. At least one abnormal point worse than mild relative loss in FDT was detected in over 90% of the abnormal hemifields equal to or worse than stage 2 of Aulhorn's classification modified by Greve, but it was 55% and 65% in stages 0-1 and 1, respectively. Nerve fiber layer defects were found in 67% of the hemifields, which was judged as abnormal in FDT but normal in HFA. CONCLUSION: FDT is useful for detection of glaucomatous visual field defects in stage 2 or worse. FDT may detect early glaucomatous visual field defects overlooked in HFA testing.

The Gly367Arg mutation in the myocilin gene causes adult-onset primary open-angle glaucoma.

PURPOSE: To present the phenotype of a family whose members showed the Gly367Arg mutation in the myocilin gene and developed primary open-angle glaucoma (POAG). METHODS: The proband developed POAG when she was 45 years old. Examination of the myocilin gene revealed that the patient had a mutation causing amino-acid change (Gly367Arg) in the myocilin gene. The available family members were given clinical and genetic examinations. RESULTS: Eight members of this family carried the same mutation. The age of disease onset of POAG in these patients with the mutation averaged 36.7 years. Four young members with the mutation, with an average age of 20.8 years, had not yet developed POAG. CONCLUSION: The Gly367Arg mutation of the myocilin gene in the pedigree causes the development of POAG in adulthood.

Molecular cloning of the bovine MYOC and induction of its expression in trabecular meshwork cells.

PURPOSE: Myocilin gene (MYOC) was identified as one of the disease-causing genes of primary open-angle glaucoma. This study was conducted to establish a system for the investigation of the biological role of MYOC in vitro by using bovine eyes, which are easy to obtain and have been widely used to examine the aqueous outflow system. The cDNA sequence of the bovine MYOC was determined and its expression in bovine eyes was examined with a quantitative polymerase chain reaction (PCR) assay. METHODS: Bovine MYOC cDNA was obtained from cultured bovine trabecular meshwork cells, and part of its sequence was determined using a primer pair designed based on the known sequence of the human MYOC gene. The 3' and 5' ends of this sequence were determined using the method of 3' and 5' rapid amplification of cDNA ends. The induction of the MYOC gene in cultured bovine trabecular meshwork cells after exposure to dexamethasone was quantitatively examined with real-time quantitative PCR using a probe designed according to the sequence of the determined bovine MYOC gene. RESULTS: Bovine MYOC protein was composed of 490 amino acids, which was 81.6% identical with that of human MYOC protein. Most of the amino acid residues of which mutation was reported to cause glaucoma were conserved in the bovine MYOC protein. After 2 weeks of treatment with 500 nM dexamethasone, expression of bovine MYOC mRNA was amplified 14-fold (14.1+/-5.1-fold, mean +/- SEM) measured by real-time quantitative PCR. CONCLUSIONS: The cDNA sequence of the bovine MYOC gene had a high degree of similarity to that of the human MYOC gene. Investigation of the function of bovine MYOC may contribute to identifying the role of MYOC protein in the aqueous outflow system.

Comparison of diclofenac and fluorometholone in preventing cystoid macular edema after small incision cataract surgery: a multicentered prospective trial.

PURPOSE: To compare a nonsteroidal topical solution (0.1% diclofenac) to a steroidal topical solution (0.1% fluorometholone) in preventing cystoid macular edema (CME) and disruption of the blood-aqueous barrier. METHODS: A multicentered, prospective clinical trial was performed on eyes undergoing phacoemulsification followed by implantation of a foldable acrylic intraocular lens by the envelope technique. The presence and degree of cystoid macula edema (CME) was determined by fluorescein angiography. A breakdown of the blood-aqueous barrier was determined by laser flare-cell photometry. RESULTS: Five weeks after surgery, CME was present in 3 of 53 eyes (5.7%) receiving diclofenac and in 29 of 53 eyes (54.7%) receiving fluorometholone. This difference was statistically significant (P < .001). The amount of flare in the anterior chamber at 3 days, 1, 2, 5, and 8 weeks after surgery was also significantly lower (P < .01-P < .001) in the diclofenac group. The degree of flare at 3 days, 1, 2, 5, and 8 weeks after surgery was significantly higher in eyes with CME (P < .001). CONCLUSIONS: These findings suggest that diclofenac effectively prevents CME following cataract surgery and that CME is closely related to the breakdown of the blood-aqueous barrier.

The relationship between visual disability and visual scores in patients with retinitis pigmentosa.

PURPOSE: To evaluate the relationship between visual disability and visual scores in patients with retinitis pigmentosa. METHODS: The relationship between visual disability and visual scores (visual acuity and visual field) was investigated in 93 patients with retinitis pigmentosa. The visual disability of each patient was evaluated using a questionnaire (a total of 35 questions, in 7 sections, regarding daily life). The reproducibility and validity of the data obtained by the questionnaire had been established by a similar investigation in glaucoma patients. Mean (+/-SD) age of patients was 52.6 +/- 15.1 years, the mean visual acuity of the logarithm of the minimum angle of resolution (log10MAR) was 0.5 +/- 0.4, and the mean deviation of visual field with the Humphrey Field Analyzer program 30-2 was -22.0 +/- 10.9 dB. RESULTS: The visual acuity of log10MAR in the better eye (r = 0.66 to 0.81) and the mean sensitivity within the central 10 degrees of the visual field (r = -0.76 to -0.62) had a definite relationship to the visual disability index of each section and their sum (P < .0001). This relationship was also confirmed in multiple regression analysis, which showed a high correlation coefficient (R2 = 0.57 to 0.77, P < .0001). CONCLUSIONS: The retinal sensitivity within the central 10 degrees and the visual acuity of log10MAR in the better eye had a significant influence on a patient's daily life. We suggest that in patients with retinitis pigmentosa, visual disability in daily life can be precisely evaluated with the retinal sensitivity within the central 10 degrees and the visual acuity in the logarithm of the minimum angle of resolution in the better eye.

Usefulness of gaze tracking during perimetry in glaucomatous eyes

Purpose: To evaluate the usefulness of a new fixation monitoring system called gaze tracking in the perimetry of glaucomatous eyes. Subjects and Method: We studied the visual field of 106 eyes in 106 persons, comprising 74 eyes with open-angle glaucoma and 32 eyes with ocular hypertension. Perimetry was performed using a Humphrey Visual Field Analyzer 740/750 with a 30-2 full threshold program. We used two parameters for gaze tracking: the percentage of the time when the subject's eye deviated from the fixation target more than 3 degrees (G 3) and 6 degrees (G 6). These parameters were assessed in three groups: those with no visual field defect (group N), those with absolute visual field defect including the blind spot (group M 1), and others (group M 0).Result: The values of G 3 and G 6 were significantly correlated with the fixation loss in groups N and M 0 (P <.01). These values were not significantly correlated with the fixation loss in group M 1 (P.10). When the fixation loss was less than 20%, G 3 and G 6 values were significantly higher in group M 1 than in groups N or M 0.Conclusion: Gaze tracking is a useful fixation monitoring system particularly in the presence absolute visual field defect including the blind spot.

Immunohistochemical localization of MYOC/TIGR protein in the trabecular tissue of normal and glaucomatous eyes.

PURPOSE: To examine immunohistochemically the localization of myocilin/trabecular meshwork inducible glucocorticoid response (MYOC/TIGR) protein in the glaucomatous and normal trabecular meshworks. METHODS: Trabecular tissues were used from one eye with late-onset goniodysgenetic glaucoma, three with primary open angle glaucoma (one of which had the MYOC/TIGR gene mutation), two with exfoliation glaucoma and one without glaucoma. For light microscopic immunohistochemistry, frozen sections were stained by the avidin-biotin complex method using anti-MYOC/TIGR polyclonal antibody. For electron microscopic immunohistochemistry, the pre-embedding method using the same antibody was performed. Double immunostaining using both anti-MYOC/TIGR and anti-type VI collagen antibodies was done by the immunofluorescence method. RESULTS: With light microscopy, immunoreactivity was seen in the whole trabecular meshwork of each of the specimens. No notable differences were detected in staining among the types of glaucoma, or between the eyes with and those without the gene mutation. Under electron microscopy, immunoreaction products were observed not only in the cytoplasm of the trabecular cells but also in the extracellular matrix, where staining was associated with the long-spacing collagen, fine granular materials and possibly microfibrils. With double immunohistochemistry, MYOC/TIGR was colocalized with type VI collagen in the trabecular meshwork. CONCLUSIONS: In glaucomatous and normal trabecular meshworks, the MYOC/TIGR protein is distributed in the extracellular matrix colocalizing with type VI collagen.

[Usefulness of gaze tracking during perimetry in glaucomatous eyes].

PURPOSE: To evaluate the usefulness of a new fixation monitoring system called gaze tracking in the perimetry of glaucomatous eyes. SUBJECTS AND METHOD: We studied the visual field of 106 eyes in 106 persons, comprising 74 eyes with open-angle glaucoma and 32 eyes with ocular hypertension. Perimetry was performed using a Humphrey Visual Field Analyzer 740/750 with a 30-2 full threshold program. We used two parameters for gaze tracking: the percentage of the time when the subject's eye deviated from the fixation target more than 3 degrees (G 3) and 6 degrees (G 6). These parameters were assessed in three groups: those with no visual field defect (group N), those with absolute visual field defect including the blind spot (group M 1), and other (group M 0). RESULT: The value of G 3 and G 6 were significantly correlated with the fixation loss in groups N and M 0 (p < 0.01). These values were not significantly correlated with the fixation loss in group M 1 (p > 0.1). When the fixation loss was less than 20%, G 3 and G 6 values were significantly higher in group M 1 than in groups N or M 0. CONCLUSION: Gaze tracking is a useful fixation monitoring system particularly in the presence of absolute visual field defect including the blind spot.

Risk factors for the progression of treated primary open-angle glaucoma: a multivariate life-table analysis.

BACKGROUND: Several factors have been reported as risk factors for the progression of primary open-angle glaucoma (POAG) but previous reports were not necessarily in agreement. We applied a multivariate life-table analysis to a large number of longitudinal data to determine the extent of the influence of various factors simultaneously. METHODS: Two hundred fifteen eyes of 215 POAG patients were included. The follow-up period ranged from 24 to 134 months (average 82.7 months). The visual field stage was determined separately in upper and lower hemifields according to the classification of Aulhorn (modified by Greve). The progression was defined as an irreversible increase of the stage in at least one hemifield. The follow-up data were analyzed with the Cox proportional hazard model. RESULTS: Mean intraocular pressure (IOP) in the follow-up period and the initial visual field stage significantly affected POAG progression (P<0.05). The risk of POAG progression was calculated to double as the mean IOP increased by 4 mmHg. Eyes with the initial visual field of stage 0-1 and moderately advanced stages had a greater risk of progression than other stages. CONCLUSION: To prevent the progression of POAG, the IOP should be kept as low as possible, particularly at the early and moderately advanced stages.

Clinical phenotype of a Japanese family with primary open angle glaucoma caused by a Pro370Leu mutation in the MYOC/TIGR gene.

PURPOSE: To present the phenotype of two patients with primary open angle glaucoma (POAG) caused by a mutation of the myocilin/trabecular meshwork-inducible glucocorticoid response (MYOC/TIGR) gene. METHODS: Complete ocular examinations were performed on the 13-year-old proband, her father, mother, and sister. DNA analysis was performed to detect the mutant gene. RESULTS: The proband and her father were found to have a mutation of the MYOC/TIGR gene. Both patients carried a heterozygous mutation in the 1,109th nucleotide, which corresponds to the 370th amino acid residue of the MYOC/TIGR gene. The clinical characteristics of both patients were: (1) development of POAG at an early age, (2) high peaks of intraocular pressure. and (3) poor response to medical treatment. CONCLUSIONS: The phenotype of these patients with a mutation of the MYOC/TIGR gene agreed with reports of other patients with mutations at other loci in this gene. The discovery of the MYOC/TIGR gene not only makes early detection of glaucoma possible, but also presents a new direction for investigating the pathogenesis of glaucoma.

Effects of oral brovincamine on visual field damage in patients with normal-tension glaucoma with low-normal intraocular pressure.

PURPOSE: To prospectively study the effect of oral brovincamine, a relatively selective cerebral vasodilator, on further deterioration of visual field in patients with normal-tension glaucoma (NTG) with low-normal intraocular pressure (IOP). METHODS: Fifty-two patients with NTG (average age 57.7 years) with an IOP that was consistently less than 15 mmHg were randomly assigned to receive oral brovincamine (20 mg three times daily) or to an untreated control group. The groups were prospectively followed for 2 years with visual field examinations every 4 months, using the 30-2 Humphrey perimeter program. Changes in mean deviation (MD), corrected pattern standard deviation (CPSD), and total deviation (TD) at 74 test points were analyzed using regression analysis with linear mixed model. Data from one eye without media opacity of each subject were analyzed. RESULTS: There were no differences between groups in age; sex distribution; refraction; blood pressure; baseline IOP; MD, CPSD, or TD at each point. Changes in MD (standard error [SE]) during the study period were -0.778 (0.178) and -0.071 (0.195) dB/year in the control and brovincamine groups, respectively; change in the control group was significantly more negative than in the brovincamine group. Change in CPSD (SE) was 0.032 (0.015) and 0.004 (0.016) dB/year in the control and brovincamine groups, respectively. Change in the control group was significantly positive, but the intergroup difference was not significant. Change in TD was significantly negative at six test points in the control group, whereas no points showed a significant trend in the brovincamine group; the intergroup difference was significant. The average IOP was 13.2 mmHg and 13.1 mmHg in the control and brovincamine groups, respectively, and there was no significant intergroup difference. CONCLUSION: Oral brovincamine may retard further visual field deterioration in patients with NTG who have low-normal IOP.

[The relationships between visual disability and visual scores in patients with retinitis pigmentosa].

PURPOSE: To evaluate the relationship between visual disability and visual scores in patients with retinitis pigmentosa. METHODS: The relationship between visual disability and visual scores (visual acuity and visual field) were investigated in 93 patients with retinitis pigmentosa. The visual disability of each patient was evaluated using a questionnaire (a total of 35 questions in 7 sections regarding daily life). Reproducibility and validity of the questionnaire had been established by an investigation in glaucoma patients. The mean (+/- standard deviation) age of patients was 52.6 +/- 15.1 years, the mean visual acuity (log10 MAR) was 0.6 +/- 0.4, and the mean deviation of visual field with Humphrey program 30-2 was -21.1 +/- 10.0 dB. RESULTS: The visual acuity in the better eye (r = 0.66-0.81) and the mean sensitivity within the central 10 degrees of the visual field (r = -0.76(-)-0.62) had a definite relationship to the visual disability index of each section (section DI) and their sum (total DI) (p < .0001). This relationship was also confirmed in stepwise multiple linear regression analysis which showed a high correlation coefficient (R2 = 0.57-0.77, p < .0001). CONCLUSIONS: Besides the visual acuity, the mean sensitivity within the central 10 degrees of the visual field is important in evaluating the visual disability of patients with retinitis pigmentosa.

Clinical evaluation of SITA: a new family of perimetric testing strategies.

PURPOSE: To perform a clinical comparison of the Humphrey Full Threshold strategy with its intended replacement, SITA Standard, regarding testing time, reproducibility, and measured threshold sensitivity in normal subjects and glaucoma patients. METHODS: Thirty-eight healthy volunteers and 80 patients with primary open-angel glaucoma underwent central 30-2 testing with both Full Threshold and SITA strategies using a Humphrey HFA 2 Model 740 perimeter. The testing time, reproducibility, and measured threshold sensitivity of the two strategies were compared. RESULTS: The testing time for measurements with SITA was 56% lower in normal subjects and 45% lower in glaucoma patients than with Full Threshold. Cases having higher mean sensitivity or cases requiring longer testing time for Full Threshold had a greater percentage reduction in testing time for SITA. The test-retest variability studied in normal subjects was lower, but not significantly so, with SITA (2.9%) than with Full Threshold (3.4%). The mean sensitivities of SITA were higher (1 dB) than those of Full Threshold not only in normal subjects but also in glaucoma patients. This higher sensitivity in SITA was found irrespective of the order of the two tests both in normal subjects and glaucoma patients. Analysis by each testing point revealed that the difference was not dependent on the test point position or the sensitivity at the point. CONCLUSION: SITA has greater patient acceptability than the Full Threshold strategy. However, the difference in sensitivity can be considerable in a serial comparison of one patient's fields tested by Full Threshold and SITA.

[Preventive effects of diclofenac ophthalmic solution on post-cataract-surgical cystoid macular edema].

Using eyes undergoing phacoemulsification followed by implantation of a foldable acrylic intraocular lens (IOL) designed for small-incision cataract surgery, a multi-center study was performed to compare a non-steroidal ophthalmic solution (0.1% diclofenac) to a steroidal ophthalmic solution (0.1% fluorometholone) in preventing cystoid macular edema (CME) and inducing disruption of the blood-aqueous barrier determined by laser flare cellmetry. The incidence of CME, noted in 3 out of 53 eyes (5.7%) receiving diclofenac and in 29 out of 53 eyes (54.7%) receiving fluorometholone, was significantly lower in the diclofenac group. The flare in the anterior chamber was also significantly lower in the diclofenac group; when compared between eyes with and without CME, the amount of flare was significantly higher in the former group. These findings suggest that diclofenac effectively prevents CME following cataract surgery and that CME is closely related to the breakdown of the blood-aqueous barrier.