Repeated administration of inhibitors for ion pumps reduce markedly tumor growth in vivo.

INTRODUCTION: Measurements of extracellular pH show that the micro environment of malignant tumors is more acidic than that of normal cells, whereas pH does not differ appreciable in normal and malignant cells. The acid micro environment of tumors is created by the secretion of tumor factors and ATP hydrolysis in hypoxic tumor tissue. In order to survive in a low pH-environment tumor cells develop regulatory mechanisms which keep their intracellular pH stable. Two of the most important systems are the Na+/H+ ion pump and the Na-dependent HCO3-/Cl- pump of stilbenian derivatives. MATERIAL AND METHODS: Experiments were carried out on DBA mice of both sexes at the age of 4 month. Laboratory animals were grown in our institute and supplied with food and aqua ad libitum. RESULTS: After termination of the experiments the mean tumor diameter in the control group was 12.4 +/- 0.8mm, in group A it was 6.9 +/- 0.6mm, and in group B we measured 6.6 +/- 3.1mm. At the final day the tumor size in treated animals was twice as small as in the control group. In addition we observed the rate of survival. In the control group only 18% of the animals were still alive at day 18. Considering the rate of survival a statistically significant difference between treated and untreated animals was observed. The survival of tumor cells is dependent on the function of these ion pumps which keep their intracellular pH values constant in the setting of an acid extracellular environment. CONCLUSION: The activity of the ion pump is especially important at the beginning of cell division and in cell proliferation. Our in vivo experiments demonstrate that prolonged administration of intratumoral ion pump inhibitors suppresses tumor growth as well as enhances survival of tumor-bearing animals. Research of inhibitors of ion pumps and their action in tumor growth opens new perspectives into pathophysiology of malignant tumors and may create new therapeutic options.

Comparing two techniques of panretinal photocoagulation on visual acuity on patients with proliferative diabetic retinopathy.

We wanted to examine which of two panretinal photocoagulation (PRP) techniques, classical panretinal photocoagulation (CPRP) and modifield peripheral panretinal photocoagulation PPRP), causes less decline of visual acuity (VA) due to macular edema (ME) in patients with proliferative diabetic retinopathy (PRD). This clinical study includes 180 eyes with PDR with initial papillar neovascularization. The patients were divided into two groups according the RP. PPRP and CPRP showed the decline of VA in all patients, more pronounced in the CPRP group after one week. After three and six months, with CPRP and PPRP the values of VA was stabilized. The result suggests that eyes with PDR and starting epipapillar neovascularisation should be treated with PPRP with priority given to CPRP because it caused better VA.

Phacoemulsification in eyes with posterior polar cataract.

The aim of the study was to evaluate the results of phacoemulsification in eyes with posterior polar cataract and to assess the risk factors for posterior capsular rupture during phaco surgery. This prospective study included 13 patients (14 eyes) undergoing phacoemulsification surgery with intraocular lens implantation. Intact posterior capsule was present in 10 (71.5%) eyes, posterior capsular rupture in 4 (28.5%) eyes, one of them with vitreal loss and requiring anterior vitrectomy. Of the eyes with intact posterior capsule, 5 (35%) had capsular plaque which was removed by gentle aspiration; in one case posterior capsulorrhexis was performed to remove the plaque; and postoperative capsule was clear in 4 (28.5%) eyes. In 3 eyes with capsular rupture, there was soft nucleus and capsular opacification greater than 3 mm in diameter, and the patients were under 40 years old. One capsular rupture occurred in dense cataract. The incidence of posterior capsular rupture in our study was 28.5%; other authors reported the incidence between 7.1% and 36%. Many different techniques have been described by other surgeons to avoid capsular rupture; however, in our opinion, posterior capsular rupture could not be avoided in some cases. In our study, the risk factors for capsular rupture in posterior polar cataract were soft nucleus with large capsular opacification and younger patient age. Our results of visual acuity after phacoemulsification in posterior polar cataracts are consistent with those reported by other authors: in 9 eyes, visual acuity was 0.8 or more (Snellen chart), and in 5 eyes there was no satisfactory improvement of visual acuity, probably due to amblyopia because the majority of the cataracts were unilateral. Accordingly, phacoemulsification in posterior polar cataracts, when done carefully, leads to good postoperative results and good visual improvement in most cases.

Incidence of acute angle-closure attacks in Split-Dalmatia County, Croatia.

The aim of the study was to determine the incidence of acute angle-closure attacks among residents of the Split-Dalmatia County, Croatia, during a 6-year period. In this retrospective, interventional case series study, hospital records of 53 consecutive patients (33 female, mean age 71.7 +/- 16.6 and 20 male, mean age 66.2 +/- 23.2) with acute angle-closure attacks, treated at University Department of Ophthalmology, Split University Hospital Center, Split, Croatia, from January 2002 to December 2007 were reviewed. The annual incidence of acute angle-closure attacks was 2 cases per 100,000 (95% CI, 0-3.4). The incidence of acute angle-closure was 0.6 (95% CI, 0-1.4) cases/100,000 per year. The incidence of acute angle-closure glaucoma was 1.5 (95% CI, 0-2.8) cases/100,000 per year. The incidence was 1.5 (95% CI, 0-3.4) cases/100,000 per year in males and 2.3 (95% CI, 0-4.6) in females. Nine (17%) patients were treated by medicamentous therapy, peripheral iridectomy was performed in 19 (36%) patients and laser iridotomy in 16 (30%) patients, whereas nine (17%) patients underwent filtering surgery. Median time between the onset of symptoms to presentation at the hospital was two days (range 1-21 days). There was no statistically significant association between the acute angle-closure attacks and seasonal variation (chi2-test = 4.6; p = 0.20). In conclusion, the number of patients with acute angle-closure attacks in the Split-Dalmatia County is relatively small; however, the significant incidence of acute angle-closure glaucoma could pose a social and health care problem in the County.

Role of NMO-IgG in distinguishing the type of optic neuritis.

PURPOSE: To emphasize the importance of neuromyelitis optica (NMO)-immunoglobulin G (IgG) antibodies testing in patients with typical optic neuritis (ON) refractory to steroid treatment. METHODS: Two patients were evaluated with ON refractory to steroid therapy and poor visual acuity; they were tested for NMO-IgG antibodies. RESULTS: Brain magnetic resonance imaging was normal in both patients. The serum and cerebrospinal fluid were positive for NMO-IgG antibodies. Magnetic resonance imaging of the cervical and thoracic spine revealed lesions longer than three vertebral segments and the diagnosis of NMO was confirmed. Treatment with plasma exchange and immunosuppressive therapy resulted in marked improvement of visual acuity. This improvement was sustained. CONCLUSIONS: The testing for NMO-IgG antibodies is important for distinguishing ON in NMO from multiple sclerosis in cases of ON refractory to steroid treatment. These cases suggest that testing for NMO-IgG antibodies should be performed in comparative trials on a larger series.

Importance of circulating platelet aggregates and haemodynamic changes in ophthalmic artery and progression of visual field loss at pseudoexfoliation glaucoma.

The aim of this work is to examine the role of circulating platelet aggregates (CPA) at pseudoexfoliation glaucoma (PXG), haemodynamic changes in the ophthalmic artery by ultrasonic color Doppler, searching for visual field progression. Vascular component at PXG and its role in VF progression dynamics has not been sufficiently explained, as well as CPA influence to ischaemic events related to optic nerve damage and VF progression. The examination included 80 patients, where of 35 (44%) men average age 68.3 +/- 7.0 and 45 (56%) women average age 65.7 +/- 7.0 (t = 1.66; p = 0.101). Forthy of them suffered from primary open angle glaucoma (POAG) as a control group (healthy), and 40 from pseudoexfoliative glaucoma (PXG) as an experimental group. All the examinees underwent complete ophthalmological examination: visual acuity, ocular fundus, intraocular pressure measured, anterior eye segment biomicroscopy with gonioscopy performed. Also VF examination was performed three times at 6 months intervals. Laboratory testing of CPA proportion values was performed by means of Wu an Hoak method and ultrasonic measurement of blood perfusion in the carotid tree, particularly concerning ophthalmic artery by means of color Doppler. Obtained decreased values of CPA proportion resulted in hypercoagulability of blood in PXG group. At PXG were also found increased blood flow resistivity indexes in ophthalmic artery (RI AO) and internal carotid artery (RI ACI), resulting with ischemia and hypoxia and finally progression of the visual filed damage. In conclusion, our study shows that examining CPA and ultrasonic monitoring of vascular parameters in ophthalmic artery with color Doppler may be the way of better understanding the vascular role in PXG prognosis.

[Dr. Juraj Curin: founder of Ophthalmology Department in Split]. / Dr. Juraj Curin: osnivac Ocnog odjela u Splitu.

The paper describes the life and work of an ophthalmologist, Juraj Curin (Gdinj, 1887 - Split, 1947). In 1921, he founded Department of Ophthalmology in Split, although permanent ophthalmologic service had existed at the Old City Hospital in Split from 1902. Dr. Juraj Curin headed Department of Ophthalmology from 1921 till 1936. He graduated from the Prague School of Medicine in 1914 and served residency in ophthalmology in Zagreb in 1921. In 1923, he attended the course on biomicroscopy at University Department of Ophthalmology in Zagreb, organized by Professor L. Koeppe and Professor A. Botteri. Dr. Curin performed a vast range of ophthalmologic surgeries for cataract, glaucoma, strabismus, oculoplastic surgery, dacryocystectomy, retinal detachment, etc. Dr. Curin was also head of trachoma service he founded in 1923. He wrote a scientifically instructive booklet on trachoma and several other papers. From 1923 till 1935, he was the only ophthalmologist in Split. Until 1926, he occasionally was going to Dubrovnik for his private practice there. Between two World Wars, he was working at the Institute of Public Health, Social Insurance Eye Service, for active population in Split. During World War II, he was active in the National Liberation Movement. In 1925, he was treasurer of the Doctors' Free Organization of Dalmatia, and in 1931 auditor at the main board of the Croatian Medical Chamber in Split. Besides his doctor practice, he was also very active in social and political life.

Safety and efficacy of monotherapy change to fixed combination (travoprost 0.004%/timolol 0.5%) in 6 months follow up period.

PURPOSE: To assess the safety and efficacy of changing antiglaucoma therapy to the travoprost 0.004%/timolol 0.5% (TTFC) fixed combination from previous monotherapies. METHODS: Prospective, open-label, observational, multicenter cohort. A change was done from prior monotherapy at day 0 to TTFC dosed once a day, regardless in the evening or in the morning, without washout period. Active evaluation of systemic and local tolerability (adverse events), and efficacy. i.e., intraocular pressure (IOP) lowering was done at control 1 (day 30), control 2 (day 90) and control 3 (day 120). RESULTS: 40/155/170 patients (79/309/339 eyes) completed the study (120 days/ 90 days/baseline, respectfully). At control 1 excluded were patients with low tolerability (severe hyperemia (6 patients), discomfort (4), chest pain (1)) and non responders (IOP lowering less than 15% from baseline IOP or target IOP >18 mmHg (4 patients)). Mean IOP at control 1 was 15.92 +/- 1.85 mm Hg (21.66% reduction) for 155 patients (non responders excluded), at control 2 was for 155 patients 15.67 +/- 2.17 mm Hg (21.14% reduction), and at control 3 for 40 patients 16.28 +/- 1.59 mm Hg (19.86% reduction). At control 2 analysis of IOP reduction by 4 groups of previous monotherapy (timolol 0,5% (N = 33/66), latanoprost 0.005% (N = 49/98), betaxolol 0.5% (N = 30/60), and travoprost 0.004% (N = 43/85) was performed. 40 patients/79 eyes endured to control 3 (after day 90 free samples were not available for all patients). Analysis of IOP reduction by 4 groups of previous monotherapy medications was performed (timolol 0.5% (N = 7/14), latanoprost 0.005% (N = 14/28), betaxolol 0.5% (N = 7/14), travoprost 0.004% (N = 12/23)). CONCLUSIONS: Changing patients from prior monotherapy to TTFC can provide on average a further reduction in IOP, while demonstrating a favorable safety profile.

[Dr Erwin Treu--the first permanent ophthalmologist in Split]. / Dr. Erwin Treu--prvi stalni oftalmolog u Splitu.

Dr. Erwin Treu (Kotor, 1875-Skopje, 1937) was the first permanent ophthalmologist in Split, Croatia. He finished his ophthalmological specialization at the Eye Clinic in Prague in 1900 at W.P. Czermak. He originates from Tirol. Dr. Treu led and organized ophthalmological service in Split and worked from 1902 to 1921 in the Split Hospital, and had a private practice until 1923. From 1904 to 1910 he temporarily worked outside Split, in Sibenik, Zadar, Dubrovnik, Kotor and Cetinje. During the First World War he was a military doctor in Split and Trogir. He performed ophthalmological operations, cataracts, glaucomas (iridectomy), strabismus (tenotomies), ocular adnexa, injuries, trachoma etc. In 1923 he left for Skopje where he at first worked as a medical major in Military Hospital, and after that as a primarius in Civil Hospital at the Department of Ophthalmology till the end of his life.

The effect of travoprost 0.004% as an adjuvant to timolol 0.5% therapy.

The aim of the study was to compare the efficacy of travoprost 0.004% eye drops added to therapy with timolol 0.5%. The study included 40 patients (80 eyes) with open angle glaucoma and intraocular pressure (IOP) above 18 mm Hg treated with topical beta blocker (timolol 0.50% twice a day). Travoprost 0.004% was added to timolol 0.5% therapy once daily in the evening. Follow up examinations were scheduled at 7 days, one month and three months. IOP lowering was achieved in all patients. Substantial lowering of 2.42 mm Hg was achieved after the first week of treatment. Further lowering and stabilization of IOP was recorded at three months, with total IOP decrease of 3.97 mm Hg; the difference was statistically significant (chi2=6.7743; p<0.01). At three months, target IOP was recorded in 64 eyes (16.4+/-0.7 mm Hg) and failed to be achieved in 16 eyes (21.1+/-2.3 mm Hg). Mild hyperemia was found in two patients and discrete hyperemia in 26 patients. Burning sensation associated with the use of travoprost 0.004% eye drops was reported by 68 patients. In conclusion, the use of travoprost 0.004% eye drops resulted in successful lowering of IOP and achievement of target IOP.

[Additive therapy with carboanhydrase inhibitors for open angle glaucoma previously treated with timolol 0.5% drops]. / Dodatno lijecenje glaukoma otvorenog kuta inhibitorima karboanhidraze na vec postojece lijecenje timololom.

Inhibitors of carboanhydrase (ICA) in the form of dorzolamide 2% drops and brinzolamide 1% drops are in use for 8-10 years, with a significant intraocular pressure (IOP) lowering effect. The goal of the present study was to obtain precise data on the efficacy of local ICA in conjunction with timolol 0.5% drops, and to evaluate the incidence of side effects. This was a prospective study that lasted 2 years and included 110 patients. Initial IOP values, before therapy with ICA, amounted to 19 +/- 8.4 mm Hg in group A and 20.5 +/- mm Hg in group B. Although the results obtained demonstrated statistically significant lowering of IOP (in group A by 4.5 +/- 2.4 mm Hg, and in group B by 4.6 +/- 2.1 mm Hg) after therapy with ICA, the difference between the groups was not found. Dorzolamide more frequently caused local side effects like aching, itching and pain in the eye. Aditional lowering of lOP in our patients was somewhat greater than reported before (4.6:4.3). Side effects (itching, aching, pain) were three times more frequent in the group treated with dorzolamide than reported by other authors; this difference could be due to patient age, as our patients were mostly elderly people and the data are subjective. The results of this study suggested the effectiveness of additional local therapy with ICA in patients with open angle glaucoma.

[The loss of visual field after proliferative diabetic retinopathy treatment with two different techniques of panretinal photocoagulation]. / Gubitak perifernog vidnog polja nakon terapije proliferacijske dijabeticne retinopatije dvjema razlicitim tehnikama panretinalne fotokoagulacije.

UNLABELLED: Diabetic retinopathy (DR) is the most common cause of blindness in the active population of industrialized countries. Panretinal argon laser photocoagulation (PRP) is used in the treatment of proliferative diabetic retinopathy. Despite its usefulness, the mentioned treatment has some side effects such as permanent visual field damage. The treatment was performed with two PRP techniques, peripheral panretinal photocoagulation (PPRP) and central panretinal photocoagulation (CPRP). Peripheral visual fields defects were assesed with Vaughans method. The aim of the study was to determine the extent of visual field defects entailed by the two different PRP techniques. RESULTS: Visual field loss in percentage was greater in the group treated with PPRP (mean 9.09 +/- 6.36%) than in group treated with CPRP (mean 4.9 +/- 4.5%) (p = 0.000037). The initial functional DR severity and presence of risk factors that influence DR severity were similar in the two treatment groups. Different results were mostly attributable to the PRP techniques employed, being significantlly less favorable with PPRP.

[Traumatic carotid-cavernous fistula]. / Traumatska karotidno-kavernozna fistula.

Carotid-cavernous fistula is uncommon consequence of craniocerebral trauma. Earlier recognition of the patients with carotid-cavernous fistula and shorter time of delay in treatment could save patients from complications and vision loss. A 27-year-old man presented with severe craniocerebral injury after an car accident. He required emergent craniotomy for an open depressed cranial fractures, haemostasis and epidural hematoma. Three months later, the patient began to exhibit progressive chemosis and proptosis of left eye. Computed tomography and cerebral angiography revealed findings consistent with a carotid-cavernous fistula. Angiography revealed a fistula between carotid artery and the cavernous sinus. The patient was treated by transarterial embolization resulting in immediate and permanent occlusion of the fistula and improved visual acuity after six months follow-up. Posttraumatic carotid-cavernous fistula may be treated successfully with the use of transarterial coil embolization.

[Cyclocryocoagulation in treatment of neovascular glaucoma]. / Ciklokriokoagulacija u lijecenju neovaskularnoga glaukoma.

Neovascular glaucoma (NVG) is a pathological condition of the eye with fast deterioration, accompanied with eyeball pain and loosing sight. The aim of the study was to examine the efficacy of cryotherapy in the treatment of NVG which is resistant to medical and surgical therapy, concerning intraocular pressure (IOT) and eyeball pain immediately after the treatment and 6 months after. In the Department of Ophthalmology, Split University Scool of Medicine, during three years 70 patients with NVG, which were resistant to medical and surgical treatment, were included in the prospective study. There were 50 males and 21 women, average age 74 +/- 6.94 (45-87). The patients were treated with transconjuctival cyclocryocoagulation, machine ERBOKRYIO AE-ERBE was used. The average value of IOT was: at admission 44.8 mmHg, 7 days after the treatment 30.7 mmHg with the tendency of falling down 30 and 90 days later, to finally 19.9 mmHg 180 days after the treatment. The IOT was significantly lower after the treatment. At admission, the average value of eyeball pain intensity was high (4.2), 7 days after the treatment it was 2.1 with the tendency of falling down to finally 1.1 180 days after the treatment. The eyeball pain intensity was significantly lower after the treatment. Cyclocryocoagulation is a method of choice in the treatment of NVG resistant to medical and surgical treatment. Cyclocryocoagulation, as a treatment of noncontrolled progressive NVG, does not have any effect on the improvement of sight in these patient.

[Disorders of color vision]. / Poremecaji kolornog vida.

This review gives a summary of all colour vision disorders (dyschromatopsias) and diagnostic methods and tests. Colour vision is inadequately treated in current literature with regard to the choice of diagnostic methods and the interpretation of results for a single disorder, which contributes to wrong dyschromatopsia diagnosing seen every day in specialist practice. Examination for colour disorders is usually outpatient and is carried out by ophthalmology or neurology departments or occupational health services under the supervision of an ophthalmologist to prevent misinterpretation of results and wrong occupational choices. The problem is very serious, and proper education should be able to provide guidelines for correct and early diagnosis of dyschromatopsia. As the examination is not well defined, it is very important to set unique criteria in diagnosing any single colour vision disorder.