Kanjiro Masuda

DOUBLE-MASKED TRIAL OF CYCLOSPORIN VERSUS COLCHICINE AND LONG-TERM OPEN STUDY OF CYCLOSPORIN IN BEHÇET'S DISEASE

The efficacy and safety of oral cyclosporin 10 mg/kg per day in Behçets disease were compared in a randomised double-masked study with those of colchicine, 1 mg orally per day, and were also investigated in a long-term open study. The double-masked study showed that cyclosporin was effective in treating not only the ocular manifestations of Behçets disease but also oral aphthous ulcer, dermal lesions, and genital ulceration. Efficacy did not weaken during long-term treatment.

A Clinical Trial of FK506 in Refractory Uveitis

We performed a clinical open trial to evaluate the efficacy and the adverse side effects of a single therapy with FK506 in refractory uveitis as a multicenter study in Japan. Fifty-three patients (41 patients with Bechçets disease, five with Vogt-Koyanagi-Harada disease, four with idiopathic retinal vasculitis, and three with other forms of uveitis) were enrolled in the study. FK506 was given orally for 12 weeks. Treatment with FK506 exhibited therapeutic effects in a dosage-dependent manner: the effectiveness was 38% in patients treated with an initial dosage of 0.05 mg/kg of body weight per day, 60% with 0.10 mg/kg of body weight per day, 83% with 0.15 mg/kg of body weight per day, and 79% with 0.20 mg/kg of body weight per day. Overall efficacy with dosage adjustment when needed was 76.5% at the conclusion of the study at the end of the 12th week. The FK506 therapy induced a variety of adverse side effects, the incidence of which depended on the dosage. The major side effects were renal impairment (28.3%, 15 of 53 patients), neurologic symptoms (20.8%, 11 of 53 patients), gastrointestinal symptoms (18.9%, ten of 53 patients), and hyperglycemia (13.2%, seven of 53 patients). The trough level of FK506 in the whole blood correlated with both the efficacy of the therapy and with the incidence of adverse effects. It is recommended to maintain the trough level between 15 and 25 ng/ml. On the basis of these results, a daily dosage of 0.10 to 0.15 mg/kg of body weight per day was suggested as an appropriate therapeutic dosage for refractory uveitis.

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.

Current Trends in Cataract and Refractive Surgery in Japan: 1996 Survey

A fifth annual survey was carried out by mail in February 1997 to investigate the current trends in cataract and refractive surgery in Japan. A questionnaire was sent to 867 ophthalmologist members of the Japanese Society of Cataract and Refractive Surgery. Data received from 440 (50.7%) of the recipients were cross-analyzed and compared with those from the previous surveys. For cataract surgery, there have been trends toward more surgical procedures performed by a surgeon, shorter period of hospitalization, and increased number of outpatient surgery. Ninety percent of respondents preferred phacoemulsification, 42% employed the self-sealing wound closure technique, and 26% used topical anesthesia for phacoemulsification. As for refractive surgery, surgeons remained rather conservative, with 26% and 6% of surgeons doing astigmatic keratotomy and refractive keratotomy, respectively.

Behcet's Disease Associated With one of the HLA-B51 Subantigens, HLA-B* 5101

The strong association of Behçets disease with HLA-B51 in several ethnic groups is well known. Because the HLA-B51 antigen has been recently identified to comprise three alleles, HLA-B* 5101, HLA-B* 5102, and HLA-B* 5103, we sought to investigate whether there is any correlation of one particular allele among them with B51-positive patients with Behçets disease. Forty-six Japanese patients with Behçets disease and HLA-B51 were typed by using the alloantisera, which allowed the subdivision of B51 antigen by the microlymphocyte toxicity assay. All the patients were found to carry HLA-B* 5101. This result suggests that amino acid substitutions at residue 167 or 171 prevent the development of Behçets disease, because HLA-B* 5101 differs from HLA-B* 5102 and HLA-B* 5103 by single amino acid substitution at residues 171 and 167, respectively, or that another non-HLA gene tightly linked to the HLA-B* 5101-associated haplotype around the HLA class I gene region is responsible for the susceptibility to Bechçets disease. This study provides insight into the molecular mechanism underlying an HLA association with Behçets disease.

Cellular autoimmunity to retinal specific antigens in patients with Behçet's disease.

The notion that autoimmune mechanisms play a role in the pathogenesis of certain uveitic conditions in humans is supported by the observation that lymphocytes from such patients respond in culture against retinal specific antigens which are uveitogenic in animals. A large proportion of uveitis patients with Behçets disease are reported to respond well to S antigen, to interphotoreceptor retinoid binding protein (IRBP) and to several of their uveitogenic peptides, in particular, the S antigen derived peptide M. Patients with Behçets disease without ocular involvement were reported not to differ in their responses to S antigen from the responses in the control group, yet 35% of them responded to IRBP and approximately two thirds of them responded to the peptides (peptide M, peptide N, R-4, or R-14). The responses were inhibited by monoclonal antibodies to CD4 and to class II MHC HLA-DR molecules. The presence of lymphocyte responses to retinal antigens in patients with Behçets disease without uveitis might indicate a preclinical stage of ocular involvement. Thus, these data support the idea that autoimmunity to retinal specific antigens may play a role in the ocular inflammation in Behçets disease.

Epidemiological Features and Visual Prognosis of Behçet's Disease ☆

PURPOSE Retrospective evaluation of epidemiological features and visual prognosis of patients with Behçets disease (BD) who visited the University of Tokyo Hospital between 1974 and 1993. OBSERVATIONS During the survey period, more than 100 new patients with BD visited the uveitis clinic in each 5-year period. The number of new patients decreased in the most recent 5-year period from 1989 to 1993. Although BD has always been more prevalent in men, the percentage of women has increased to 24.7% (19/77) in the most recent 5-year survey period. The percentage of patients who initially manifested ocular symptoms in their third or fourth decade was more than 70%. The proportion of the incomplete type of BD gradually had increased to 62.3% (48/77) by 1993. Among the extraocular major symptoms, oral aphtha and skin lesions have been frequent and genital ulcer has become less frequent in the last 20 years. The patients whose visual acuity was better than 0.4 at the first visit in the 1984-1993 period had a significantly better visual prognosis than the patients in the previous 10-year period. The main drug therapy consisted of colchicine and cyclophosphamide in the earlier 10-year period, and of colchicine and ciclosporin in the later 10-year period. CONCLUSIONS Behçets disease is still one of the most frequently encountered types of endogenous uveitis. There have been some changes in the epidemiological features of the patients with BD over the past 20 years. The introduction of ciclosporin in 1985 is probably responsible for the improvement of the visual prognosis in BD patients.

Polymerase Chain Reaction for the Detection of the Varicella-zoster Genome in Ocular Samples From Patients With Acute Retinal Necrosis

We used the polymerase chain reaction to detect the virus genome in ocular samples from patients with clinically diagnosed acute retinal necrosis. Four samples from four patients with acute retinal necrosis, and five samples from three patients with other ocular diseases (sarcoidosis, rhegmatogenous retinal detachment, and epiretinal membrane of unknown origin) were evaluated. The samples consisted of aqueous humor, vitreous, or subretinal fluid. Primers were specific for varicella-zoster virus, herpes simplex virus, or cytomegalovirus. The varicella-zoster virus genome was detected in three of the four samples from patients with acute retinal necrosis. Among these three positive samples, two had PstI-site-less point mutation, strains that have been described only in Japan and of low prevalence. Samples from patients with diagnoses other than acute retinal necrosis yielded negative results when varicella-zoster virus primer was used. No sample was positive for herpes simplex virus or cytomegalovirus primers.

Effects of topical nipradilol, a β blocking agent with α blocking and nitroglycerin-like activities, on intraocular pressure and aqueous dynamics in humans

AIMS To study the effects of topical nipradilol, a non-selective β blocker with α blocking and nitroglycerin-like activities, on intraocular pressure (IOP) and aqueous humour dynamics in normal humans and in patients with ocular hypertension. METHODS Nipradilol (0.06%, 0.125%, 0.25%, 0.5%) was applied to normal volunteers (n = 12) to test for IOP lowering effects. In a second group of normal volunteers (n = 11), nipradilol (0.125% and 0.25%) and timolol (0.5%) were compared for IOP lowering effects. After a single administration of 0.25% nipradilol, IOP, flare intensity in the anterior chamber, aqueous flow, uveoscleral outflow, tonographic outflow facility, and episcleral venous pressure were either directly measured or mathematically calculated. Topical nipradilol (0.25%) was administered to 24 patients with ocular hypertension twice daily for 8 weeks. RESULTS Administration of 0.25% nipradilol decreased IOP with a maximum reduction of 4.2 mm Hg lasting 12 hours. A single instillation of both 0.25% nipradilol and 0.5% timolol reduced the IOP in normotensive human subjects to the same degree. A single instillation of 0.25% nipradilol decreased the aqueous flow rate in the treated eye by 20%. Nipradilol produced no significant effect in tonographic outflow facility or episcleral venous pressure, but uveoscleral outflow was increased. In patients with ocular hypertension, twice daily instillation of 0.25% nipradilol decreased IOP without tachyphylaxis for the 8 week test period. CONCLUSION Topical nipradilol (0.25%) reduced IOP by decreasing the aqueous flow rate and probably also by increasing uveoscleral outflow. Nipradilol should be further investigated as a new antiglaucoma drug.

Clinical evaluation of UF-021 (Rescula; isopropyl unoprostone).

We have reviewed two Phase III clinical studies of isopropyl unoprostone conducted in Japan: a 12-week comparative study of 0.12% isopropyl unoprostone and 0.5% timolol, and a 52-week administration of two concentrations of isopropyl unoprostone in ocular hypertensive and primary open-angle glaucoma patients. These studies showed a similar ocular hypotensive effect of 0.12% isopropyl unoprostone to 0.5% timolol and a sustained ocular hypotensive effect of the drug for up to one year. Adverse reactions of isopropyl unoprostone were minor and similar to those of timolol. No pigmentary changes of the irides were noticed. In view of these results, isopropyl unoprostone seems to be a useful antiglaucoma medication.