Complement factor H and LOC387715/ARMS2/HTRA1 variant's frequencies and phenotypic associations in neovascular age-related macular degeneration, a pilot study.

PURPOSE: To evaluate the frequency of 12 single nucleotide polymorphisms (SNPs) of complement factor H (CFH) and LOC387715/ARMS2/HRTA1 and their association with some of the presenting clinical features of neovascular age-related macular degeneration (AMD). METHODS: In this prospective non-comparative case series forty four naïve patients with neovascular AMD were genotyped using sequencing or Sequenom iPLEX technology. Descriptive tests were used for displaying the magnitude of each allele, gender distribution, and age at diagnosis. Fisher exact test was used to evaluate the correlation between visual acuity (VA) and different alleles. Also Kruskal-Wallis test was used for comparison between age at the time of diagnosis and different alleles. RESULTS: The most frequent SNP among studied patients was rs1061147 with 100% frequency rate. The least common was rs2672598 with a frequency of 52.27%. Only the allele rs800292 of CFH locus on 1q32 was associated with VA better than 20/200 (p value = 0.034). The frequency of this allele was 77.27% (34 patients) in this study. There was no significant association between any of alleles, and VA worse than 20/200(p > 0.05). Fifteen patients had bilateral exudative AMD (34.09%). There was no significant difference between alleles in bilateral neovascular AMD and unilateral disease. Also bilateral and unilateral patients were not different in terms of age, gender or VA (p value: 0.330, 0.764 and 0.456 respectively). There was also no significant association between any of SNPs and bilaterality of disease. CONCLUSION: We designated the frequencies of SNPs of CFH and LOC387715/ARMS2/HRTA1 in neovascular AMD in a sample of Iranian patients. Only the allele rs800292 of CFH locus on chromosome 1q32 was associated with better VA.

Thermoanalytical characterization of clindamycin-loaded intravitreal implants prepared by hot melt extrusion.

BACKGROUND: The aim of the present study was to evaluate a non-destructive fabrication method in for the development of sustained-release poly (L, D-lactic acid)-based biodegradable clindamycin phosphate implants for the treatment of ocular toxoplasmosis. MATERIALS AND METHODS: The rod-shaped intravitreal implants with an average length of 5 mm and a diameter of 0.4 mm were evaluated for their physicochemical parameters. Scanning electron microscopy (SEM), differential scanning calorimetry (DSC), Fourier-transform infrared (FTIR), and nuclear magnetic resonance (1H NMR) studies were employed in order to study the characteristics of these formulations. RESULTS: Drug content uniformity test confirmed the uniformity in different implant batches. Furthermore, the DSC, FTIR, and 1H NMR studies proved that the fabrication process did not have any destructive effects either on the drug or on the polymer structures. CONCLUSION: These studies showed that the developed sustained-release implants could be of interest for long-term sustained intraocular delivery of clindamycin, which can provide better patient compliance and also have good potential in terms of industrial feasibility.

Design and development of intraocular polymeric implant systems for long-term controlled-release of clindamycin phosphate for toxoplasmic retinochoroiditis.

BACKGROUND: The release of the anti-toxoplasmosis drug, clindamycin phosphate, from intraocular implants of the biodegradable polymers poly (D, L-lactic acid) (PLA) and poly (D, L-lactide-co-glycolide) (PLGA) has been studied in vitro. MATERIALS AND METHODS: The preparation of the implants was performed by a melt-extrusion method. The developed extrudates were characterized and compared in in-vitro release profiles for elucidating the drug release mechanism. The formulations containing up to 40% w/w of drug were prepared. Release data in phosphate buffer (pH 7.4) were analyzed by high performance liquid chromatography. The release kinetics were fitted to the zero-order, Higuchi's square-root, first order and the Korsmeyer-Peppas empirical equations for the estimation of various parameters of the drug release curves. Degradation of implants was also investigated morphologically with time (Scanning Electron Microscopy). RESULTS: It was observed that, the release profiles for the formulations exhibit a typical biphasic profile for bulk-eroding systems, characterized by a first phase of burst release (in first 24 hrs), followed by a phase of slower release. The duration of the secondary phase was found to be proportional to the molecular weight and monomer ratio of copolymers and also polymer-to-drug ratios. It was confirmed that Higuchi and first-order kinetics were the predominant release mechanisms than zero order kinetic. The Korsmeyer-Peppas exponent (n) ranged between 0.10 and 0.96. This value, confirmed fickian as the dominant mechanism for PLA formulations (n ≤ 0.45) and the anomalous mechanism, for PLGAs (0.45 < n < 0.90). CONCLUSION: The implant of PLA (I.V. 0.2) containing 20% w/w of clindamycin, was identified as the optimum formulation in providing continuous efficient in-vitro release of clindamycin for about 5 weeks.

Development, characterizations and biocompatibility evaluations of intravitreal lipid implants.

BACKGROUND: The treatment of posterior eye diseases is always challenging mainly due to inaccessibility of the region. Many drugs are currently delivered by repeated intraocular injections. OBJECTIVES: The purpose of this study was to investigate the potential applications of natural triglycerides as alternative carriers to synthetic polymers in terms of drug release profile and also biocompatibility for intraocular use. MATERIALS AND METHODS: In vitro/in vivo evaluations of intravitreal implants fabricated from the physiological lipid, glyceride tripalmitate containing clindamycin phosphate as a model drug was performed. The micro-implants with average diameter of 0.4 mm were fabricated via a hot melt extrusion method. The extrudates were analyzed using scanning electron microscopy, differential scanning calorimetry, and in vitro drug dissolution studies. For biocompatibility, the implants were implanted into rabbit eyes. Clinical investigations including fundus observations, electroretinography as well as histological evaluations were performed. RESULTS: In vitro tests guaranteed usefulness of the production method for preparing the homogenous mixture of the drug and lipid without affecting thermal and crystalinity characteristics of the components. In vitro releases indicated a bi-phasic pattern for lower lipid ratios, which were completed by the end of day three. With higher lipid ratios, more controlled release profiles were achieved until about ten days for a lipid ratio of 95%. Clinical observations did not show any abnormalities up to two months after implantation into the rabbit eye. CONCLUSIONS: These results suggest that although the implant could not adequately retard release of the present drug model yet, due to good physical characteristics and in vivo biocompatibility, it can represent a suitable device for loading wide ranges of therapeutics in treatment of many kinds of retinochoroidal disorders.

Sharp-object-induced open-globe injuries in Iranian children admitted to a major tertiary center: a prospective review of 125 cases.

UNLABELLED: Ocular trauma in children can result in catastrophic visual and psychological outcomes both for the child and his/her family. According to the WHO, childhood blindness is one of the major causes of avoidable blindness and so target of the Vision 2020 program. To achieve this program's goals, it is necessary to explore the epidemiological patterns of ocular trauma in different countries which in its turn could be a valuable means to guide us in developing preventive measures. Our study is a hospital-based prospective study which was conducted to reveal detailed information about children who were admitted to a large tertiary care hospital with the diagnosis of lacerating globe injury due to a sharp object. PATIENTS AND METHODS: During a 6-month period (December 2006 to June 2007), 125 eyes of 125 children (age ≤16 years) with the diagnosis of open-globe injury were enrolled. Clinical data were documented. Demographic data and details of the event were explored and documented based on the study questionnaire (adopting the Birmingham Eye Trauma Terminology and the United States Eye Injury Registry model as basis) by interviewing the parents and the child. RESULTS: The mean age was 8.5 years (SD = 4.36 years, range: 1-16). The boys:girls ratio was 2.5:1; this ratio was age dependent, showing a significant increase with age. The home was the most frequent place (61.7%) for the trauma to occur in. Most traumas (50%) occurred in the afternoon (12 midday to 6 p.m.). Almost half of the traumas were unintentional self-injuries and occurred when the child was alone. A knife and fireworks were the two most frequent causes of injury. CONCLUSION: As the home is the most common place of ocular trauma in this age group and as lack of proper supervision and accessibility of sharp objects such as knives are the background of the event in most cases, it is strongly recommended to educate parents about providing a safe environment at home for their children. Work-related eye injuries in this age group should also be reduced by regulations for prohibiting children's work or at least providing the necessary education and safety goggles.

Medullary thyroid carcinoma with metastasis to iridocorneal angle, a case report / 国际眼科杂志(Guoji Yanke Zazhi)

AIM:To report a rare case of medullary thyroid carcinoma (MTC) with iridocorneal angle metastasis.METHODS:A 28-year-old woman,a known case of sporadic MTC was referred to our hospital due to left eye mass involving iridiocorneal angle.Several months' later retinal evaluation revealed retinal involvement with some patches.RESULTS:After palliative laser photocoagulation ablation of the choroidal and angle lesions no signs of recurrence or any new lesion was detected.CONCLUSION:As we know this is the first report of MTC with iridocorneal angle metastasis in the literature.

Therapeutic effect of macular grid photocoagulation in treatment of nonexudative age-related macular degeneration.

BACKGROUND: To investigate the effect of prophylactic subthreshold laser macular grid photocoagulation on drusen area and to evaluate the visual outcome and incidence of choroidal neovascularization in patients with soft drusen maculopathy. METHODS: In a nonrandomized nonmasked clinical trial, 18 patients (36 eyes) with bilateral soft drusen maculopathy were studied. For each patient, one eye was treated with 48 subthreshold (invisible end-point) applications of 532-nm KTP-laser in a macular grid pattern and the fellow eye was observed. Soft drusen areas were calculated and compared between the two groups at baseline and follow-up visits at 3, 6, 12, and 30 months of therapy. Best corrected visual acuity was also compared in observed and laser-treated eyes. Reduction of drusen area, change in visual acuity, and rate of CNV were assessed in both groups. RESULTS: At baseline, there was no significant difference in the mean drusen surface area between the two groups (P = 0.90). The mean surface area of soft drusen in treated eyes was 6.51 mm(2) after 30 months and 7.58 mm(2) (P = 0.50) in the control eyes. There was a trend towards reduction in the mean soft drusen area after 30 months from baseline in laser-treated eyes (6.51 vs. 6.97 mm(2)). In treated eyes, there was no statistically significant difference between the mean best corrected visual acuity at the baseline (0.28 logMAR) and after 30 months (0.32 logMAR) (P = 0.40). CONCLUSION: Subthreshold macular grid photocoagulation with 532-nm KTP-laser did not seem to reduce drusen surface area significantly and did not improve best corrected visual acuity after 30 months. No exudative lesion developed in laser-treated eyes.