PRIMARY OPEN-ANGLE GLAUCOMA DUE TO MUTATIONS IN THE MYOC GENE.

AIM: Mutations in the myocilin gene (MYOC) cause trabecular dysfunction and thus are involved in the pathogenesis of primary open-angle glaucoma (POAG). The aim of this study was to characterize and describe the clinical findings in two Czech families with POAG due to pathogenic variants in the MYOC gene. MATERIAL AND METHODS: Members of the two families affected by POAG underwent complete ophthalmological examination. In the proband from the first family, a direct sequencing of the three most frequent mutations in the MYOC gene was performed, and in the proband from the second family, an exome sequencing was performed. Other family members underwent targeted tests using direct sequencing. RESULTS: In total, 10 individuals diagnosed with POAG aged 20-70 years (mean 32.2 years, SD ±10,9 years) were examined. Eight of them showed advanced glaucomatous neuropathy with severe changes in the retinal nerve fiber layer. Clinical signs of POAG were present in six individuals in the third decade of life already; another four developed POAG during the fourth decade of life. Eight out of 10 patients had to undergo filtration surgery. Surgery was performed within 1 to 7 years of diagnosis, but mostly was performed within 2 years of glaucoma diagnosis. In the first family, MYOC variant c.1099G>A p.(Gly367Arg) was shown in the affected family members; in the second family MYOC variant c.1440C>A p.(Asn480Lys), both in heterozygous state. The changes were assessed as pathogenic. CONCLUSION: Our study is the first to describe mutations in the MYOC gene causing POAG in Czech patients. Genetic testing may be recommended for this diagnosis, especially in individuals with early presentation and a positive family history. Carriers of pathogenic variants of the MYOC gene have a lifetime risk of developing POAG of more than 50% and the course of their disease is often more aggressive, requiring surgical intervention to permanently control the intraocular pressure.

Acute elevation of intraocular pressure in patient with hyperlipidemic myeloma.

PURPOSE: To introduce a rare case of patient with hyperlipidemic myeloma and ocular manifestation in form of masquerade syndrome with acute elevation of intraocular pressure (IOP) and hyperviscous retinopathy. RESULTS: 55-year-old man with newly diagnosed hyperlipidemic myeloma and hyperviscous syndrome was acutely referred to our glaucoma outpatient clinic due to problems with his left eye: sudden pain, blurred vision, redness of the eye and IOP of 44 mm Hg. We excluded attack of angle closure glaucoma and found presence of whitish material in the anterior chamber and blood obstructing the iridocorneal angle. Glaucoma therapy was initiated and lavage of the anterior chamber of the left eye with sampling of the aqueous humour for biochemical and cytological examination was performed. Identification of trace amount of cryoprotein in the samples of humour proved diagnosis of masquerade syndrome. Finding of the hyperviscous retinopathy and nonperfusion of wide peripheral areas of retina in both eyes was indicated to laser coagulation of these areas. The patient underwent in the meantime three times plasmapheresis, four cycles of biological therapy and autologous stem cell transplantation reaching complete remission of the myeloma. Local and systemic therapy led to significant clinical finding improvement on the anterior segment and fundus of both eyes. CONCLUSIONS: Masquerade syndrome can be complicated by acute elevation of IOP. Diagnostic lavage of the anterior chamber, local therapy, systemic therapy and close interdisciplinary cooperation contributed to right diagnosis, IOP normalisation, ocular and general condition improvement.

Clinically relevant interactions of anti-apoptotic Bcl-2 protein inhibitors with ABC transporters.

In this work we studied clinically relevant interactions between the BH3 mimetics and the ABCB1 and ABCG2 transporters. We observed that the intracellular levels of ABT-263 and ABT-199, but not ABT-737, might be reduced by ABCB1 or ABCG2. Importantly, this effect was proportional to the transporter expression level. High transporter expression levels decreased the intracellular levels of ABT-263 and ABT-199 substantially. Low transporter expression levels, which are clinically relevant, affected the intracellular level of ABT-263 slightly but significantly, however, they failed to decrease the intracellular level of ABT-199 below the control level in parental cells. Our results further revealed that ABT-263 did not inhibit the ABCB1 mediated transport, however, it partially inhibited the ABCG2 mediated transport at clinically relevant concentrations. In contrast, ABT-199 inhibited partially the ABCB1 mediated transport and it fully inhibited the ABCG2 mediated transport at clinically relevant concentrations. Importantly, cells expressing higher drug transporters levels required higher concentrations of ABT-263 or ABT-199 to achieve certain inhibition of substrate efflux. CONCLUSIONS: Antiproliferative effects of ABT-263 and ABT-199 might be reduced by ABCB1 or ABCG2, however, this effect depends on transporter expression levels. Since the expression levels of ABCB1 and ABCG2 are rarely high in clinical samples, their contribution to the overall resistance to ABT-263 or ABT-199 is probably low. Inhibition study revealed that ABT-199, but not ABT-263, fully inhibited low expression level of ABCG2. Our data suggest that ABT-199 should be evaluated beyond its original application as an inhibitor of the ABCG2 transporter in clinical settings.

Ocular surface injuries in autoimmune dry eye. The severity of microscopical disturbances goes parallel with the severity of symptoms of dryness.

Autoimmune dry eye (Sjögren's syndrome, SS) is a chronic systemic disease characterized by salivary and lacrimal gland inflammation and tissue damage leading to keratoconjunctivitis sicca and xerostomia. In this review attention has been devoted to the cause of the development of oxidative injuries of the ocular surface of patients suffering from SS. It was shown that lacrimal glands and diseased conjunctival epithelium reveal increased expression of pro-inflammatory cytokines which are released into the tear fluid. A high amount of pro-inflammatory cytokines highly induce the elevated expression and activity of enzymatic systems that generate reactive oxygen and nitrogen species. An abundant amount of these toxic products leads to a decrease in antioxidants and to the formation of cytotoxic related oxidants, such as peroxynitrite. All these factors, together with reactive oxygen species from polymorphonuclear leukocytes, contribute to the development of oxidative injuries at the ocular surface. From the clinical point of view it is important that the level of severity of the above described microscopical disturbances found in conjunctival epithelial cells goes parallel with the level of severity of dry eye symptoms.

[Implantation of anterior chamber lenses]. / Implantace prednekomorových cocek.

From January 1989 till July 1993 85 anterior chamber lenses were implanted at the 1st Department of the 1st Medical School of the Charles University in Prague. In 30 cases the anterior chamber lenses were implanted primarily and in 55 cases as a secondary procedure. In all cases flexible lens of Kelman type was used. The incidence of postoperative complications was almost the same as was described in literature. The complications were less frequent after secondary implantations. After more extent loss of vitreous during extracapsular cataract extraction it is recommended to delay the implantation of anterior chamber lens at least after half a year. Final visual acuity 6/6-6/12 was achieved in 70% primary and in 85.5% secondary implantations.

[Levobunolol HCl--a beta-blocker produced by the firm Allergan]. / Levobunolol HCL--betablokátor firmy Allergan.

Vistagan is a new beta-blocker produced by Allergan that is used for treatment of glaucoma. The results of a clinical trial with 18 patients with open-angle glaucoma, previously treated with Timoptol, are presented. Vistagan was as effective as Timoptol in reducing the intraocular pressure and was better tolerated by patients.

[Glaucoma in the Czech Republic]. / K problematice glaukomu v Ceské republice.

The authors investigated the conditions for the diagnosis and treatment of glaucoma in the Czech Republic using questionnaires dispatched to 88 departments. The total number of patients suffering from glaucoma is 50,000, the highest rate being in Prague and Moravia (à 9,000). In relation to the number of population the frequency is greatest in Prague (1 per 140 population) and lowest in Southern Bohemia (1 per 318). In 12 departments routine gonioscopic examinations are not made, in 30 departments applanation measurements of the intraocular pressure are not made. Statistical computed perimetry can be performed only in six departments. In 1989 about one tenth of the total number of 9,000 patients hospitalized on account of glaucoma were hospitalized on account of acute glaucoma. In that year 952 primary and 320 secondary glaucomas were operated, the greatest number in Prague and Eastern Bohemia. It is essential to improve the standard of ambulatory diagnostic and therapeutic care at the expense of hospital admissions.

[Laser microsurgery in glaucoma]. / Laserová mikrochirurgie glaukomu.

Based on ten years work, the authors summarize their experience with the use of different types of lasers and laser methods in the treatment of glaucomas. They draw attention to the limits of effectiveness of laser microsurgery, to different modifications of hitherto used methods and their combinations. The authors try to define the position of lasers in the therapy of glaucomas.

[Biocompatibility of retropupillary intraocular lenses]. / Biokompatibilita retropupilárních nitroocních cocek.

The authors give an account on the incidence of two types of reactions in the early postoperative period (within two weeks) after implantation of retropupilar intraocular lenses. In a group of 320 patients they observed them in 51 (16%) incl. 17 diabetics. In the group of diabetic patients the incidence of reactions was twice as frequent. A typical fibrin reaction starting on the third day after operation was recorded in 18 patients (5%), in the remaining 33 patients (11%) there was increased opalescence of the aqueous humour, and exudation of cels and cellular structures to the lens surface was associated with the surgical trauma, in particular in beginner implantologists. The two mentioned types of reactions do not have a substantial influence on the final functional effect.

[A comparative study of various methods of measuring intraocular pressure]. / Srovnávací studie ruzných zpusobu merení nitroocního tlaku.

The authors compare measurement of intraocular pressure by aplanation, impression and contact-free tonometry. They draw attention to the advantages of contact-free tonometry in screening of glaucoma which is a reliable, rapid and simple method.

[Working ability of patients with various forms and stages of glaucoma]. / Moznosti pracovního zarazení nemocných s ruznými formami a stadii glaukomu.

Authors evaluated the questionnaries filled by patients with glaucoma of different type treated on the Prague Second Eye Clinic. These were completed by clinical data as state of visual functions and modes and course of the treatment. Different types of glaucoma were present: open-angle glaucoma (74), angular glaucoma (34), pigmentary glaucoma (12), exfoliative glaucoma (4), congenital glaucoma (13). Operations were performed in 26.5% of eyes, laser trabeculoplasty 18.8% and laser irodotomy 15.7%, and pharmacotherapy was applied in remaining patients. Ocular disease was the cause of the change of employment in 11.6%, the total disability pension and the partial one, were acknowledged in 3.6% and, 6.6%, resp. On contrary to the previous data, the number of patients with working disability was significantly decreased in comparison with the previous data. This fact could be explained by the use of the non-miotic antiglaucomatics, laser surgery, microsurgical operations and more precise diagnostics of the earlier stages of glaucoma.