Photoprotection and photoreception of intraocular lenses under xenon and white LED illumination.

OBJECTIVE: To analyze the photoprotection and phototransmission that various intraocular lenses (IOLs) provide under the illumination of a xenon (Xe) lamp and white LEDs (light emitting diode). METHODS: The spectral transmission curves of six representative IOLs were measured using a Perkin-Elmer Lambda 35 UV/VIS spectrometer. Various filtering simulations were performed using a Xe lamp and white LEDs. The spectral emissions of these lamps were measured with an ILT-950 spectroradiometer. RESULTS: The IOLs analyzed primarily show transmission of nearly 100% in the visible spectrum. In the ultraviolet (UV) region, the filters incorporated in the various IOLs did not filter equally, and some of them let an appreciable amount of UV through. The Xe lamp presented a strong emission of ultraviolet A (UVA), and its emission under 300nm was not negligible. The white LED did not present an appreciable emission under 380nm. CONCLUSIONS: The cut-off wavelength of most filters is between 380 and 400nm (Physiol Hydriol60C(®), IOLTECH E4T(®), Alcon SA60AT(®), Alcon IQ SN60WF(®)), so that their UV protection is very effective. Nonetheless, the IOL OPHTEC Oculaid(®) contains a filter that, when a Xe lamp is used, lets through up to 20% for 350nm and up to 15% for 300nm, which at this point is ultraviolet B (UVB). The OPHTEC(®) Artisan IOL has a transmission peak below 300nm, which must be taken into account under Xe illumination. White LEDs do not emit energy below 380nm, so no special protection is required in the UV region.

Spectral transmission of the pig lens: effect of ultraviolet A+B radiation.

OBJECTIVE: To determine the spectral transmission curve of the crystalline lens of the pig. To analyse how this curve changes when the crystalline lens is irradiated with ultraviolet A+B radiation similar to that of the sun. To compare these results with literature data from the human crystalline lens. PROCEDURES: We used crystalline lenses of the common pig from a slaughterhouse, i.e. genetically similar pigs, fed with the same diet, and slaughtered at six months old. Spectral transmission was measured with a Perkin-Elmer Lambda 35 UV/VIS spectrometer. The lenses were irradiated using an Asahi Spectra Lax-C100 ultraviolet source, which made it possible to select the spectral emission band as well as the intensity and exposure time. RESULTS: The pig lens transmits all the visible spectrum (95%) and lets part of the ultraviolet A through (15%). Exposure to acute UV (A+B) irradiation causes a decrease in its transmission as the intensity or exposure time increases: this decrease is considerable in the UV region. CONCLUSIONS: We were able to determine the mean spectral transmission curve of the pig lens. It appears to be similar to that of the human lens in the visible spectrum, but different in the ultraviolet. Pig lens transmission is reduced by UV (A+B) irradiation and its transmission in the UV region can even disappear as the intensity or exposure time increases. An adequate exposure intensity and time of UV (A+B) radiation always causes an anterior subcapsular cataract (ASC).

Lipoic acid lessens Th1-mediated inflammation in lipopolysaccharide-induced uveitis reducing selectively Th1 lymphocytes-related cytokines release.

Inflammation results in the production of free radicals. We evaluated the anti-inflammatory and antioxidant capacity of lipoic acid in an experimental uveitis model upon a subcutaneous injection of endotoxin into Lewis rats. The role of oxidative stress in the endotoxin-induced uveitis model is well-known. Besides, the Th1 response classically performs a central part in the immunopathological process of experimental autoimmune uveitis. Exogenous sources of lipoic acid have been shown to exhibit antioxidant and anti-inflammatory properties. Our results show that lipoic acid treatment plays a preventive role in endotoxin-induced oxidative stress at 24 h post-administration and reduced Th1 lymphocytes-related cytokines by approximately 50-60%. Simultaneously, lipoic acid treatment caused a significant reduction in uveal histopathological grading and in the protein concentration in aqueous humors, but not in cellular infiltration.

Ultraviolet radiation at Mediterranean latitudes and protection efficacy of intraocular lenses.

PURPOSE: After determining the mean intensity of ultraviolet radiation to which the human eye is exposed at Mediterranean latitudes, this data is used to evaluate the efficacy of the ultraviolet filters incorporated into various intraocular lenses. METHODS: Ultraviolet radiation measured at Mediterranean latitudes was used as a reference for the theoretical calculation of the amount of radiation to which the human eye is exposed. The spectral transmission curve from 290 to 380 nm was measured for 10 IOLs using a UV/VIS Perkins-Elmer Lambda 800 spectrometer. RESULTS: At Mediterranean latitudes, at sea level, with a mean annual solar irradiation of 50 j/cm(2), the human eye receives a quantity of UVA and UVB that is lower than the threshold toxic dose for the rabbit crystalline lens (93 j/cm(2) for UVA and 6.45 j/cm(2) for UVB). However, at higher altitudes and with albedo approaching 0.9 (fresh snow), the amount of radiation increases, with duration of exposure potentially playing a significant role. The UV filters incorporated into the IOLs studied are, in general, protective against such levels of radiation. CONCLUSION: At Mediterranean latitudes, at sea level, the amount of UV radiation to which our eyes are exposed is insufficient to damage the crystalline lens; however, at higher altitudes, the risk of such damage exists. UV filters incorporated into intraocular lenses are generally effective, since they filter all radiation with wavelengths under 380 nm.

Identification of 14 novel mutations in the long isoform of USH2A in Spanish patients with Usher syndrome type II.

Mutations in USH2A gene have been shown to be responsible for Usher syndrome type II, an autosomal recessive disorder characterised by hearing loss and retinitis pigmentosa. USH2A was firstly described as consisting of 21 exons, but 52 novel exons at the 3' end of the gene were recently identified. In this report, a mutation analysis of the new 52 exons of USH2A gene was carried out in 32 unrelated patients in which both disease-causing mutations could not be found after the screening of the first 21 exons of the USH2A gene. On analysing the new 52 exons, fourteen novel mutations were identified in 14 out of the 32 cases studied, including 7 missense, 5 frameshift, 1 duplication and a putative splice-site mutation.

Mutation profile of the MYO7A gene in Spanish patients with Usher syndrome type I.

Usher syndrome type I is the most severe form of Usher syndrome. It is an autosomal recessive disorder characterized by profound congenital sensorineural deafness, retinitis pigmentosa, and vestibular abnormalities. Mutations in the myosin VIIA gene (MYO7A) are responsible for Usher syndrome type 1B (USH1B). This gene is thought to bear greatest responsibility for USH1 and, depending on the study, has been reported to account for between 24% and 59% of USH1 cases. In this report a mutation screening of the MYO7A gene was carried out in a series of 48 unrelated USH1 families using single strand conformation polymorphism analysis (SSCP) and direct sequencing of those fragments showed an abnormal electrophoretic pattern. Twenty-five mutations were identified in 23 out of the 48 families studied (47.9%). Twelve of these mutations were novel, including five missense mutations, three premature stop codons, three frameshift, and one putative splice-site mutation. Based on our results we can conclude there is an absence of hot spot mutations in the MYO7A gene and that this gene plays a major role in Usher syndrome.

Effect of prophylactic brimonidine on bleeding complications after cataract surgery.

PURPOSE: To evaluate the effect of prophylactic brimonidine on bleeding complications after cataract surgery. METHODS: The authors performed a prospective, double-masked, two-surgeon study of 137 patients (137 eyes) who underwent phacoemulsification and intraocular lens implantation with or without prophylactic brimonidine before cataract surgery. The authors also compared the effect of brimonidine among patients with systemic diseases such as diabetes mellitus (types I and II), hypertension, and anticoagulant or antiplatelet treatment. RESULTS: Subconjunctival hemorrhage was observed in 73.70% of the patients not treated with brimonidine before surgery and in only 23.75% of the patients who were given prophylactic brimonidine (p<0.001, chi2). The grade of hemorrhage was also statistically significant (p<0.001, Mann-Whitney). No statistically significant difference with regard to the presence of hemorrhage in diabetic patients or in the anticoagulant or antiplatelet treatment group was observed. However, a statistically significant difference (p<0.027, chi2) was found between hypertensive patients treated and not treated with prophylactic brimonidine before cataract surgery. CONCLUSIONS: This study suggests that brimonidine administered before cataract surgery may significantly reduce subconjunctival hemorrhage in the general population. It has been shown to be beneficial in hypertensive patients. A strong statistical trend, but not significance has been found in diabetic patients or in patients treated with antiplatelet or anticoagulant drugs, but further studies are needed to reach conclusive results.

Acute iridocyclitis in a patient with AIDS diagnosed as toxoplasmosis by PCR.

PURPOSE: To study the etiology of an acute iridocyclitis in a patient with AIDS using polymerase chain reaction (PCR) analysis of aqueous humor. METHODS: Case report describing a patient diagnosed with toxoplasmic retinochoroiditis in his left eye. He stopped his treatment after three weeks and subsequently developed an acute iridocyclitis without chorioretinitis in the fellow eye. Anterior chamber paracentesis was performed and aqueous humor was assayed by PCR. RESULTS: PCR of the aqueous humor showed positivity for Toxoplasma gondii. The iridocyclitis responded to topical dexamethasone and oral treatment with pyrimethamine and sulfadiazine. CONCLUSION: PCR is an effective method to diagnose toxoplasmic iridocyclitis in a patient with AIDS.

Posterior chamber silicone intraocular lens for the correction of myopia: an experimental study in rabbits.

PURPOSE: To establish whether ocular lesions arise after implantation of posterior chamber silicone intraocular lenses (IOL) for the correction of high myopia. METHODS: Twenty-three posterior chamber silicone IOL were implanted in 23 eyes of the same number of pigmented rabbits. After different follow-up time (from one week to one year) the eyes were enucleated and processed for histopathological study after determining the protein concentration in the aqueous humor. The IOL were removed for staining and examination, and adhered cells were counted. Ten eyes analogous to those operated upon were used as controls. RESULTS: Intense inflammation was observed in the early postoperative period in all cases. Protein concentration in the aqueous humor was initially high and decreased over time, though without reaching normal values at one year. Mono- and multinucleated cells were seen adhering to the IOL, though they decreased in number over time and were practically absent after one year. Friction between the posterior surface of the iris and the IOL had no clinical repercussions. The only pigment accumulations were in the iris and in the peritrabecular zone. There were no significant differences in the accumulation of granules in relation to IOL diameter or power. Excluding three cataracts morphologically similar to traumatic cataracts, five lens opacifications were observed: two were anterior subcapsular cataracts, and the other three were only precapsular deposits. The IOL had no synechiae to the ocular tissues. CONCLUSIONS: Opacification of the lens is the main concern with implanted posterior chamber silicone IOL. Larger series of eyes must be analysed to establish the true incidence and reversibility of these opacities.

Diclofenac sodium and cyclosporin A inhibit human lens epithelial cell proliferation in culture.

PURPOSE: To investigate the effect of diclofenac sodium salt and cyclosporin A (CsA) on human lens epithelial cell (HLEC) growth in culture. METHODS: Cultures of HLEC were obtained from anterior capsules from extracapsular cataract surgery. Third-passage cells were seeded in 96-well plates in 0.1 ml culture medium. Cytotoxicity was estimated by the tetrazolium test in confluent monolayers after 24 h exposure to a wide range of concentrations of diclofenac and CsA. The effect of subcytotoxic concentrations of diclofenac and CsA on HLEC proliferation in subconfluent cultures was evaluated after 24 and 72 h of exposure. To investigate the relationship between PGE2 synthesis and the inhibitory effect of these drugs, after 24 h of exposure to diclofenac and CsA the production of PGE2 was measured by radioimmunoassay. We also tested the effect of exogenous PGE2 addition to diclofenac 72-h-treated cultures. RESULTS: Diclofenac and CsA (at concentrations > or = 65 microM and > or = 2.5 microM, respectively) inhibited the proliferation of subconfluent cultures of HLEC in a dose-dependent fashion. Diclofenac inhibits PGE2 synthesis, while CsA at high doses stimulates PGE2 synthesis of cultured HLEC. Exogenous PGE2 addition reversed in part the inhibitory effect of diclofenac. CONCLUSIONS: Diclofenac and CsA at appropriate doses are effective in inhibiting cultured HLEC proliferation. This could be of interest to prevent posterior capsule opacification. Further in vivo experimental studies seem worthwhile.

Reproducibility of digital image analysis for measuring corneal haze after myopic photorefractive keratectomy.

PURPOSE: To evaluate the usefulness of digital image analysis for quantifying corneal haze by determining the reproducibility of its measurements at the corneal plane. METHODS: In a prospective study, 20 randomly selected eyes that had undergone myopic photorefractive keratectomy were photographed focusing the slit beam on their anterior corneal surface. Each photograph was examined using computer image analysis techniques that detect the edge of the reticular pattern of the image. Quantification of the difference between two areas, treated and adjacent untreated cornea, each containing 3,750 pixels with a resolution of 256 gray levels, was performed. Intra-analyzer variation was determined by evaluating the photographs obtained by two analyzers under standard conditions on four separate visits. Interanalyzer variation was calculated using one measurement and the mean of the four measurements. RESULTS: The pooled standard deviation of the measurements for the analyzers was 0.63 and 0.62 gray levels (coefficient of variation, 4.1% and 3.3%). An association between less severe haze measurements and higher reproducibility scores was found (r = .42; P = .007). The mean interanalyzer variation was smaller for the average of four measurements, 0.55 +/- 0.37 gray levels, than for one measurement, 0.94 +/- 0.73 gray levels (P = .014). CONCLUSIONS: Good reproducibility for haze measurements by digital image analysis of the differences between the treated and adjacent untreated corneal areas was obtained. When the average of four measurements was used instead of a single measurement, interanalyzer reproducibility increased significantly. This new technique may be used to quantify and analyze corneal haze after myopic photorefractive keratectomy.

Direct objective quantification of corneal haze after excimer laser photorefractive keratectomy for high myopia.

PURPOSE: The purpose of the study is to measure regional distribution differences in corneal haze after excimer laser photorefractive keratectomy for high myopia. METHODS: The authors developed computerized gradient edge detectors with which were analyzed digitized anterior slit-lamp photographs of 40 eyes, an average of 21.0 plus or minus 14.5 weeks after photorefractive keratectomy for high myopia (-6 to -22 diopters). A treated area an adjacent untreated area on the anterior corneal surface, each containing six regions, were quantified, and the difference was correlated with various parameters. RESULTS: Mean differences between scarred and clear areas for haze grade 0.5, 1.0, 2.0, 3.0, and 4.0 were 16.9, 26.6, 42.6, 60.4, and 76.4 gray levels, respectively (rs = 0.96; P = 0.0001). A low but statistically significant correlation between the intended correction and postoperative corneal haze was found (r = 0.33; P = 0.037). The mean coefficient of variation of the amount of opacification within each treated area was 9.4%. This coefficient of variation increased with a longer follow-up time (r = 0.88; P = 0.0001). The difference in the intensity of haze between the center and more peripheral regions over the entrance pupil did not correlate with the attempted correction. However, a strong association between a relatively less severe central corneal haze with respect to more peripheral haze and longer follow-up time was found (r = -0.96; P = 0.0001). CONCLUSION: The amount of corneal haze showed a weak positive association with the attempted correction in excimer laser photorefractive keratectomy for high myopia. Corneal haze appeared fairly uniformly distributed within the ablation zone, but a more heterogeneous distribution was found with a longer follow-up time. Furthermore, later postoperative examinations disclosed a clear trend toward diminishing central opacification relative to peripheral regions over the entrance pupil.

Excimer laser photorefractive keratectomy for high myopia.

One hundred and thirty-three eyes of 103 patients had photorefractive keratectomy with a slit scan mode excimer laser for myopia ranging from -6.00 to -22.00 diopters (D). The epithelium was removed with 20% ethanol, and the ablation was done with a tapered profile surrounding the optical zone. Patients were divided into two groups based on preoperative myopia: Group A, -6.00 D to -12.00 D (88 eyes); Group B, -12.50 D to -22.00 D (45 eyes). In Group A, mean preoperative refraction was -9.59 +/- 1.79 D. Mean postoperative refraction was -0.29 +/- 1.47 D at one month, -0.85 +/- 1.68 D at three months, -1.17 +/- 2.04 D at six months, and -0.56 +/- 0.74 D at one year. Anterior stromal haze was greatest at the end of the first month; it diminished thereafter. This haze did not reduce the best corrected visual acuity in any eye in Group A. Mean preoperative refraction in Group B was -14.69 +/- 5.27 D. Mean postoperative refraction was -1.34 +/- 2.02 D at one month, -0.76 +/- 2.08 D at three months, -3.88 +/- 2.32 D at six months, and -5.50 +/- 5.00 D at one year. Three eyes in Group B lost one or two lines of best corrected visual acuity as a result of severe stromal haze and epithelial scarring. Group A's results were similar to those obtained in eyes with low myopia.(ABSTRACT TRUNCATED AT 250 WORDS)

High dose intravitreal foscarnet in the treatment of cytomegalovirus retinitis in AIDS.

The efficacy and tolerance of high dose intravitreal foscarnet for cytomegalovirus retinitis in patients with AIDS was studied. Foscarnet in a dose of 2400 micrograms was injected directly into the vitreous of 11 patients (15 eyes). Five patients had active retinitis (eight eyes, 53.3%), and received a 3 week induction therapy of six injections as the first step. Six patients had initial inactive retinitis (seven eyes, 46.7%), and received only maintenance therapy which consisted of a weekly injection. The main indications for intravitreal therapy were: myelosuppression, kidney toxicity, catheter related sepsis, or refusal of intravenous therapy. The patients were followed for a mean period of 16 weeks (range 8-28 weeks) and received a total of 304 injections. Vitreous foscarnet levels were measured by high performance liquid chromatography. After a 3 week course of induction therapy, complete resolution of the active retinitis was seen in 62.5% (5/8 cases), while 37.5% (3/8 cases) had partial resolution. No cases failed to respond or progress. The rate of relapse on maintenance therapy was 33% (five of 15 eyes) by 20 weeks, and two of these eyes did not respond to reinduction and progressed in involvement of the macula or optic nerve. Neither important local complications nor intraocular drug toxicity were observed. Vitreous foscarnet levels in two different patients were 896 mumol/l and 74.9 mumol/l at 22 3/4 hours and 42 1/2 hours after the injection. Intravitreal foscarnet appears to be a safe, effective, and useful alternative in patients with intolerance to intravenous and viral therapy.

Intravitreal foscarnet for cytomegalovirus retinitis in a patient with acquired immunodeficiency syndrome.

We treated a patient who had acquired immunodeficiency syndrome and cytomegalovirus retinitis of the left eye. After anesthetic had been topically administered, the patient received intravitreal injections of 1,200 micrograms of foscarnet. Plasma and vitreous foscarnet levels were measured by high-performance liquid chromatography. Systemic absorption of the drug was not evident. Elimination half-life from the vitreous after one injection was 54.0 hours. Vitreous levels remained above the mean 50% inhibition value for cytomegalovirus for approximately 56 hours and above the mean inhibition value for human immunodeficiency virus for approximately 241 hours. The patient's visual acuity improved from 20/30 to 20/25 in the left eye. Ophthalmoscopy showed the retinal lesion to have become inactive, and no reactivation occurred during the follow-up period of more than four months. The drug was well tolerated and no retinal toxicity was evident. We suggest an induction treatment regimen of two injections weekly for three weeks, followed by a maintenance treatment regimen of one injection weekly.

Liposomally-entrapped ganciclovir for the treatment of cytomegalovirus retinitis in AIDS patients. Eperimental toxicity and pharmacokinetics, and clinical trial.

Treatment of retinitis by cytomegalovirus (CMV) in AIDS patients requires frequent repetitive injections of intravitreal ganciclovir (GCV). This study was undertaken to establish experimentally whether the intravitreal application of liposomally-entrapped GCV could prolong intraocular therapeutic levels when compared with the intravitreal injection of free GCV, and the clinical effectiveness of this approach in AIDS patients. Intraocular concentration of GCV was determined by means of an ELISA test in rabbit vitreous 2, 3, 7, and 14 days after a single intravitreal injection of either different doses of the free drug (0.2-20 mg) or 1 mg of liposomally-entrapped GCV. After 72 h, only the vitreous of rabbits injected with doses of free GCV greater than or equal to 5 mg showed therapeutic levels of the drug; no GCV was detected after 72 h with any of the doses applied. Moreover, the microscopic study revealed GCV-induced damage in retinal structures in the animals injected with a free GCV dose greater than or equal to 15 mg. Intravitreal injection to rabbits of 1 mg of liposomally-encapsulated GCV showed no retinal toxicity at any of the time points studied, and therapeutic levels were detected up to 14 days after injection (4.67 +/- 0.39 microgram/ml). Five AIDS patients suffering CMV retinitis were injected with 0.5 mg of liposomally-entrapped GCV (2 mg of lecithin). Complete remission of the CMV retinitis was observed already at the third injection of 0.5 mg GCV (one per week) and relapse did not occur during the 2-4 month follow-up of the patients. In view of the results presented, it can be concluded that intravitreal injection of liposomally-encapsulated GCV increases the time period required for reinjections in the treatment of CMV retinitis.