Effect of cysteine in transgenic mice on healing of corneal epithelium after excimer laser photoablation.

PURPOSE: To evaluate the role of prepared cysteine per os in corneal epithelial healing in transgenic mice (B6(A)-Rpe65rd12/J) after excimer laser photoablation. MATERIALS AND METHODS: In our prospective case series, 60 eyes of 30 mice had uneventful bilateral excimer laser photoablation. A first group, composed of 15 mice, received standard topical post-operative therapy with tobramycin, diclofenac and dexamethasone eyedrops, plus cysteine 5 mg 5 microg/10 microl phosphate-buffered saline (3 times a day for 1 week) per os or until corneal re-epithelialization was complete. The control group of 15 mice received standard post-operative therapy plus placebos. The mice were monitored daily, commencing the day after surgery, for 7 days to evaluate the corneal re-epithelialization rate using a video slit-lamp camera with a cobalt blue light. The mean diameters of corneal wounds were measured. Videotaped images were recorded and analysed by computer planimetry. RESULTS: All the eyes of the mice treated with cysteine healed completely by day 5 after surgery, with a mean re-epithelialization time of 92 +/- 10 h (SD); the mean re-epithelialization time was 125 +/- 8 h in eyes that received the placebo. There were no statistically significant differences between the 2 groups in corneal haze presentation during follow-up, perhaps because the time period was too brief (7 days). However, corneal clarity in the study group was greater than in the control group, as shown on slit-lamp biomicroscopy. No side effects or toxic effects were documented. CONCLUSIONS: These data suggest that cysteine significantly accelerates epithelial healing after excimer photoablation. A further clinical study should be performed to confirm the results obtained in this study, and the long-term efficacy of cysteine in preventing corneal haze.

[siRNAs with high specificity to the target: a systematic design by CRM algorithm].

'Off-target' silencing effect hinders the development of siRNA-based therapeutic and research applications. Common solution to this problem is an employment of the BLAST that may miss significant alignments or an exhaustive Smith-Waterman algorithm that is very time-consuming. We have developed a Comprehensive Redundancy Minimizer (CRM) approach for mapping all unique sequences ("targets") 9-to-15 nt in size within large sets of sequences (e.g. transcriptomes). CRM outputs a list of potential siRNA candidates for every transcript of the particular species. These candidates could be further analyzed by traditional "set-of-rules" types of siRNA designing tools. For human, 91% of transcripts are covered by candidate siRNAs with kernel targets of N = 15. We tested our approach on the collection of previously described experimentally assessed siRNAs and found that the correlation between efficacy and presence in CRM-approved set is significant (r = 0.215, p-value = 0.0001). An interactive database that contains a precompiled set of all human siRNA candidates with minimized redundancy is available at http://129.174.194.243. Application of the CRM-based filtering minimizes potential "off-target" silencing effects and could improve routine siRNA applications.

Effect of cytochrome c peroxidase on the corneal epithelial healing process after excimer laser photo-ablation in transgenic mice.

AIM: To evaluate the role of commercially prepared cytochrome c peroxidase eye drops in corneal epithelial healing of transgenic B6(A)-Rpe65rd12/J mice after excimer laser photo-ablation. MATERIALS AND METHODS: In our prospective animal series, 72 eyes of 36 mice had uneventful bilateral excimer laser photo-ablation. In each mouse, one eye received standard topical postoperative therapy with tobramycin, diclofenac, and dexamethasone eye drops plus cytochrome c peroxidase eye drops (two drops three times a day for 1 week or until corneal re-epithelialization was complete, corresponding to 15,000 IU/day). The fellow eye served as the control and received standard postoperative therapy plus placebo. The mice were monitored daily, commencing on the day after surgery, for 7 days to evaluate the corneal re-epithelialization rate using a video slit lamp camera with cobalt blue light. The mean diameter of the corneal wounds was measured. Videotaped images were recorded and analyzed by computer planimetry. RESULTS: All eyes treated with cytochrome c peroxidase eye drops healed completely before day 5 after surgery, with a mean re-epithelialization time of 92 +/- (SD) 10 h; the mean re-epithelialization time was 121 +/- 8 h in the eyes receiving placebo (p < 0.05). There were no statistically significant differences between the two groups in corneal haze presentation during the follow-up period (p = 0.70), perhaps because the observation period was too short (7 days). However, the corneal clarity, on slit lamp biomicroscopy, in the study group was higher than that in the control group. No side effects or toxic effects were observed. CONCLUSIONS: These data suggest that cytochrome c peroxidase significantly accelerates epithelial healing after phototherapeutic keratectomy. Further clinical studies should be performed to prove the results obtained in this study and the long-term efficacy of cytochrome c peroxidase to prevent corneal haze.

Tamoxifen retinopathy: does it really exist?

BACKGROUND: Tamoxifen retinopathy is known to be an adverse effect of high-dose tamoxifen treatment. Evidence of ocular toxicity at lower doses is less convincing: the aim of this study was to assess the prevalence of the above-mentioned retinopathy in a population treated with low-dose tamoxifen. METHODS: One hundred and twenty-nine women treated with low-dose tamoxifen (20 mg/day) were examined. Visual acuity measurement, slit-lamp biomicroscopy and fundus examination were performed. Patients were reexamined after 6-12 months. RESULTS: Refractile retinal opacities, similar to those previously described as tamoxifen retinopathy, were observed in four patients (prevalence 3.1%; mean duration of therapy 806 days). None of them revealed corneal opacities, papillary and/or macular edema, or visual impairment. The ophthalmoscopic aspect did not change after a mean follow-up of 215 days, although one of these patients had interrupted tamoxifen intake. Statistical analysis (Student's t-test) did not reveal any difference between patients with and those without refractile retinal opacities as far as age, treatment duration and ERG values were concerned. An early hyperfluorescence, reminescent of cuticular drusen, was demonstrated by fluorescein angiography in all four cases. CONCLUSIONS: The present study would seem to confirm that low-dose tamoxifen may induce retinal toxicity in a low proportion of patients, but we cannot be certain that the refractile retinal opacities observed are really caused by tamoxifen, as differentiation from age-related macular degeneration with cuticular drusen appears nearly impossible.

Pseudoexfoliation syndrome: a cohort study on intraoperative complications in cataract surgery.

Our aim was to determine the rate of intraoperative complications induced by pseudoexfoliation syndrome (PSX) in cataract surgery. We report our experience regarding 1,052 consecutive patients who underwent phacoemulsification. Exact logistic regression was used to examine the role of PSX in intraoperative complications. Odds ratio for intraoperative complications (vitreous loss, capsular break, zonular break) was estimated to be 5.1 for PSX present as compared to when it is absent. PSX was associated with a statistically significant increase in intraoperative complications during cataract surgery (p<0.0001).

The features of Tenon's capsule at the limbus.

Glaucomatous optic neuropathy is a multifactorial disease, whose most important risk is high intraocular pressure. Filtering surgery, i.e. trabeculectomy, is the operation of choice to lower pressure, allowing the aqueous to outflow from the anterior chamber under the conjuctiva and Tenon's capsule. Failure to establish a filtration bleb is due in most cases to subconjunctival fibrosis, leading to bleb encapsulation (Tenon's cyst). Our study aimed to locate the best cleavage plane for aqueous drainage. Based on histological data, the subtenonian space appears to satisfy this requirement, due to low scarring aptitude and low resistance.

Capsule contraction after continuous curvilinear capsulorhexis.

We report two cases of capsular bag contraction that occurred within 1 month after continuous curvilinear capsulorhexis, phacoemulsification, and intraocular lens implantation. Neither patient had a known risk for this complication. Both patients had a neodymium:YAG laser anterior capsulotomy, which disrupted the capsulorhexis margin and led to prompt capsular bag distension.

Hyperopic shift after 4-8 incision radial keratotomy: eight-year follow-up.

PURPOSE: To evaluate the prevalence, amount and possible factors connected with the hyperopic shift after radial keratotomy. BASIC PROCEDURES: We studied 86 eyes (51 patients) which underwent 4-8 incision radial keratotomy (delayed technique), consecutively performed by the same surgeon between February 1983 and November 1988. The diamond-bladed knife was set at 95% of the smallest paracentral ultrasonic corneal thickness measurement and the clear zone diameter was between 3.0 and 3.5 mm. Preoperative myopia ranged from -2.00 to -7.25 diopters (D). The average follow-up was 97.4 months (range 78 to 122 months). MAIN FINDINGS: After eight years of follow-up, the cycloplegic spherical equivalent was satisfactory: 66.2% of the eyes showed a refractive error within 0.5 D, 17.4% were myopic by more than 0.5 D and 16.2% were hyperopic by more than 0.5 D. The mean refractive error was 0.02 D (SD +/- 0.75 D). Between six months and eight years after surgery a hyperopic shift of more than 0.5 D was found in 40.6% of the eyes. The mean hyperopic shift was higher (0.78 D) in the eyes which had keratometry less than 36 D six months after surgery. Compared to the eyes with keratometry greater than 36 D (mean hyperopic shift 0.38 D), the difference was statistically significant (p < 0.02). CONCLUSIONS: These results show that keratometry, measured six months postoperatively, plays a fundamental role in the stability of postsurgical refraction, as the risk of hyperopic shift is higher in eyes with keratometry < 36 D.

Brain pathology and strabismus.

This article reviews some of the past year's important papers, with particular emphasis on interesting connections between congenital pathology of the central nervous system and infantile strabismus, neuroimaging findings in meningomyelocele sustaining A-pattern strabismus, surgical outcome in strabismic children with cerebral palsy, and oculomotor problems in cerebral vascular diseases. Oculographic findings in myasthenic ocular palsies and a new form of congenital ocular fibrosis are also reviewed.

Efficacy of transfer factor in treating patients with recurrent ocular herpes infections.

Recurrent ocular herpes is an insoluble problem for the clinician. As cellular immunity plays an important role in controlling herpes relapses, and other studies have shown the efficacy of HSV-specific transfer factor (TF) for the treatment of herpes patients, an open clinical trial was undertaken in 134 patients (71 keratitis, 29 kerato-uveitis, 34 uveitis) suffering from recurrent ocular herpetic infections. The mean duration of the treatment was 358 days, and the entire follow-up period 189,121 before, and 64,062 days after TF treatment. The cell-mediated immune response to the viral antigens, evaluated by the lymphocyte stimulation test (LST) and the leucocyte migration test (LMT) (P < 0.001), was significantly increased by the TF treatment. The total number of relapses was decreased significantly during/after TF treatment, dropping from 832 before, to 89 after treatment, whereas the cumulative relapse index (RI) dropped, during the same period, from 13.2 to 4.17 (P < 0.0001). No side effects were observed. It is concluded that patients with relapsing ocular herpes can benefit from treatment with HSV-specific TF.

Brain pathology and strabismus.

If we consider the complex and articulate organization of the oculomotor neural system, ie, infranuclear, nuclear, internuclear, and supranuclear levels, how many neuronal structures are implicated and their widespread localization in the central nervous system, and if we understand the various relationships within the oculomotor system and with other cerebral structures, we may easily realize that cerebral diseases and oculomotor disturbances are tightly and reciprocally connected. Many diseases may be associated with ocular movement impairment, sometimes acting on different sites of oculomotor organization. These alterations may have a clear pathophysiologic meaning and a relevant topographic localizing value, otherwise correlations and mechanisms are simply hypothetical. Last but not least for conceptual relevance are the modifications of neuronal anatomy and physiopathologic mechanisms induced by the strabismus. In the past year many articles have been published that analyze the relationships and the pathogenetic role of cerebral anomalies in the context of strabismus syndromes. Of outstanding interest is the proof of cortical and subcortical neural stations' plasticity, and the evidence of a cerebral anatomophysiologic basis of strabismus and amblyopia. In this context the midbrain, pontine, and brain stem nuclei and neuronal organizations have a peculiar importance. We will try to systematically expose, even if briefly, the main contributions in this area.

Transfer factor prevents relapses in herpes keratitis patients: a pilot study.

Transfer Factor is a dialysable moiety obtained from immune lymphocytes. It has been successfully used for the treatment of several viral infections including labial and genital herpes. In the present study, thirty-three patients with low immune response to HSV antigens and suffering from herpes ocular infections were orally treated with HSV-specific transfer factor (TF). Their relapse index was reduced from 20.1 before treatment to 0.51 after TF administration, with only 6/33 patients relapsing. Although this is not a placebo-controlled-randomized study, the results suggest that TF specific for HSV antigens may be efficacious for preventing relapses of ocular herpes infections as has been the case with genital and labial localisations.

The use of phosphorus magnetic resonance spectroscopy to study in vivo the effect of coenzyme Q10 treatment in retinitis pigmentosa.

Phosphorus magnetic resonance spectroscopy (31P-MRS) has emerged as a noninvasive reliable tool for in vivo study of human tissue bioenergetics. It detects and quantifies some phosphorylated compounds present in millimolar concentration inside the cell, including ATP, phosphocreatine (PCr) and inorganic phosphate (Pi). By 31P-MRS we studied brain and skeletal muscle energy metabolism of three patients with retinitis pigmentosa before and after oral coenzyme Q10 (CoQ10) (100 mg/day). Before treatment we found a low PCr content in the brains of all patients, accompanied by a high [Pi] and high [ADP]. In two of three patients CoQ10 treatment resulted in a larger brain energy reserve mainly shown by an increased [PCr]. Abnormal muscle mitochondrial function was found only in one patient as shown by a reduced rate of PCr resynthesis after exercise. In this patient CoQ10 treatment resulted in an increased rate of PCr resynthesis. Our observations indicate that CoQ10 can improve mitochondrial functionality in the brain and skeletal muscle of patients with retinitis pigmentosa.

Effects of oxygen-ozone therapy on age-related degenerative retinal maculopathy.

The effects of oxygen-ozone therapy on 20 patients affected by age-related degenerative maculopathy have been studied. Visual acuity and eye fluorangiography were the parameters used in order to evaluate the efficacy of the therapy. Medical ozone was administered intravenously according to the technique called "ozonized major autohemoinfusion", the total amount of ozone ranging from 1,500 to 2,000 micrograms per session for a 4 months period. The results have indicated that the majority of patients showed an improvement of their ocular condition, suggesting continuation of this type of investigation on a larger group of people.