Beauty versus Health-How Eyelash Extensions May Affect Dry Eye Disease?

Background: Eyelash extensions (EEs) are among the most popular cosmetic procedures today. There is no prospective study demonstrating how this procedure affects the ocular surface and eye dryness in particular. The goal of this study is to evaluate the effect of EEs removal on dry eye symptoms and signs. Materials and Methods: The subjects were prospectively recruited from routine clinical examinations for dry eye complaints. Only subjects with an OSDI score above 31 were included in the study. The subjects also planned to have the EEs removed and agreed to abstain from makeup use and new cosmetic procedures for 4 weeks. The presence of dry eye was evaluated by an OSDI questionnaire, and objectively by tear breakup time (TBUT), staining (Oxford scale) and blinking intervals. All tests for dry eye were performed at baseline and 4 weeks after EEs removal. Results: The mean age of our patients, all female, was 28 years. The size and type of EEs was diverse. The decision process was mainly based on appearance and models. None of the subjects had any health conditions. The mean result from the score from the OSDI questionnaire at the baseline was 33.4 and improved to 26.7 points 4 weeks after EEs removal. Objectively, the mean TBUT increased from 11.25 to 13.96 s. For the same period, the blinks increased by two per minute, and the staining was reduced by 1.0 grade. Conclusions: Removal of EEs improves the symptoms and the objective signs of dry eye. The most popular beauty procedure regarding eyelashes might not be innocuous to eye health.

CAPSULaser - a new modality in the portfolio of cataract surgeons.

To assess the efficiency and safety of capsulorhexis with CAPSULaser in comparison with standard capsulorhexis performed manually by emerging and established surgeons. Specialized Eye Hospital-Varna Bulgaria. Prospective, randomized, non-masked study. Patients were randomized to the M group (manual CCC), L group (laser CCC), and 2 surgeons. The manual CCC was targeted at 5.5 mm. The laser CCC was sized at 5.3 mm and measured with the same caliper device during photomicroscopy. The inclusion criteria were otherwise healthy eyes with cortical, nuclear, or subcapsular cataracts of any maturity with a biomicroscopically deep anterior chamber and preoperative pupil wider than 6.5 mm. The surgical time was measured for the entire procedure and only for capsulotomy. Sixty eyes of 60 patients, aged 65.8 ±â€…11 years, were prospectively recruited. Two surgeons (one with 3 years and one with 30 years of experience) performed the same types and number of procedures. The experienced surgeon was 2 times faster when performing manual capsulorhexis, but the time for CAPSULaser was almost the same. The size of the "laser" CCC was planned to be 5.3 and ended up with a minimum of 5.4 in 4 weeks; however, no lens prolapse from the CCC was observed. Utilization of the CAPSULaser in cataract surgery is easy and achievable for surgeons at any stage of their careers and provides controlled, well-centered capsulorhexis with no more adverse events than conventional surgery. The limitations are the requirement for a minimal pupil size of 6 mm, a deep anterior chamber, and a transparent cornea.

TFOS Lifestyle: Impact of cosmetics on the ocular surface.

In this report the use of eye cosmetic products and procedures and how this represents a lifestyle challenge that may exacerbate or promote the development of ocular surface and adnexal disease is discussed. Multiple aspects of eye cosmetics are addressed, including their history and market value, psychological and social impacts, possible problems associated with cosmetic ingredients, products, and procedures, and regulations for eye cosmetic use. In addition, a systematic review that critically appraises randomized controlled trial evidence concerning the ocular effects of eyelash growth products is included. The findings of this systematic review highlight the evidence gaps and indicate future directions for research to focus on ocular surface outcomes associated with eyelash growth products.

Damage of the ocular surface from indoor suntanning-Insights from in vivo confocal microscopy.

PURPOSE: To evaluate the ocular surface at the microstructural level of adults who habitually undertake indoor-suntanning utilising in vivo confocal microscopy. METHODS: Participants were prospectively recruited and enrolled into either а study group (n = 75) with a history UV indoor tanning, or a control group (n = 75) with no prior history of artificial tanning. The study group participated in voluntary tanning sessions performed with standard equipment and maintained their usual routine for eye protection. Slit lamp biomicroscopy and in vivo confocal microscopy were performed at baseline before undertaking a series of suntanning sessions (10 sessions of 10 min duration over a 15 day period), within three days after the last session, and four weeks after the last session. Control group participants were examined at baseline and 8 weeks later and did not participate in tanning sessions. RESULTS: All participants were female with a mean age of 25 ± 4 years and 24 ± 4 years in the study and control groups, respectively. No clinically significant changes were observed in either group over time using slit lamp biomicroscopy (all p ≥ 0.05), however, statistically significant differences were observed between the study and the control group for all corneal layers imaged using confocal microscopy (all p ≤ 0.03). Characteristic cystic conjunctival lesions with dark centres and bright borders were observed in 95% of the study group before and in 100% after the suntanning sessions. CONCLUSION: Indoor suntanning resulted in statistically significant microstructural changes in the cornea and the bulbar conjunctiva that are undetectable with slit lamp biomicroscopy.

Handing it to pterygium: Explaining pterygium laterality.

PURPOSE: To evaluate any correlation between pterygium laterality and patient handedness. METHODS: Our study represents a retrospective observational study of a series of consecutive pterygium patients recruited from two centres. Each patient was assessed for their handedness which was compared to the laterality of their presenting pterygium. Patients that possessed bilateral disease comparisons between pterygium size and handedness were made. Correlation statistics were performed to compare patient handedness and pterygium location (right or left). For patients possessing bilateral disease only, the pre-surgical differences between lengths and areas of pterygium were calculated and compared. RESULTS: A total of 219 patients were recruited into our study. 172 patients possessed unilateral disease and in 47 patients, the disease was bilateral. A significant association was identified between handedness and pterygium laterality (p < 0.001). Patients with right-sided pterygia were more likely to be right-handed (OR 2.327) and left-sided presentations who were more likely to be left-handed (OR 5.717). For bilateral presentations, patients were found to have longer (mean increase 3.50 ± 0.47 mm) and larger (mean increase 4.38 ± 0.48 mm2) pterygia in the eye ipsilateral to their dominant hand. CONCLUSIONS: A new insight of handedness as a contributing factor to pterygium laterality is consistent with evidence relating to the asymmetrical development of cortical cataract as well as to theories underlying the geometry of ocular UV exposure. A more complete understanding of factors contributing to ocular insolation may further inform as to improved protective measures and provides further evidence for the role of peripheral light focusing in pterygium pathogenesis.

TFOS European Ambassador meeting: Unmet needs and future scientific and clinical solutions for ocular surface diseases.

The mission of the Tear Film & Ocular Surface Society (TFOS) is to advance the research, literacy, and educational aspects of the scientific field of the tear film and ocular surface. Fundamental to fulfilling this mission is the TFOS Global Ambassador program. TFOS Ambassadors are dynamic and proactive experts, who help promote TFOS initiatives, such as presenting the conclusions and recommendations of the recent TFOS DEWS II™, throughout the world. They also identify unmet needs, and propose future clinical and scientific solutions, for management of ocular surface diseases in their countries. This meeting report addresses such needs and solutions for 25 European countries, as detailed in the TFOS European Ambassador meeting in Rome, Italy, in September 2019.

Exclusion of known corneal dystrophy genes in an autosomal dominant pedigree of a unique anterior membrane corneal dystrophy.

PURPOSE: With advances in phenotyping tools and availability of molecular characterization, an increasing number of phenotypically and genotypically diverse inherited corneal dystrophies are described. We aimed to determine the underlying causative genetic mechanism in a three-generation pedigree affected with a unique anterior membrane corneal dystrophy characterized by early onset recurrent corneal erosions, small discrete focal opacities at the level of Bowman layer and anterior stroma, anterior stromal flecks, and prominent corneal nerves. METHODS: Twenty affected and unaffected members of a three-generation family were examined and extensively clinically characterized including corneal topography and in vivo confocal microscopy, and biological specimens were collected for DNA extraction. Mutational analysis of two corneal genes (TGFBI [Transforming Growth factor-beta induced] and ZEB1 [zinc finger E box-binding homeobox 1]) was undertaken, in addition to testing with the Asper Corneal Dystrophy gene chip (Asper Ophthalmics, Tartu, Estonia). Subsequent Genotyping To 11 Known Corneal Gene Loci (COL8A2 [Collagen, Type VIII, Alpha-2], TACSTD2 [Tumor-Associated Calcium Signal Transducer 2], PIP5K3 [Phosphatidylinositol-3-Phosphate 5-Kinase, Type III], GSN [Gelsolin], KERA [Keratocan], VSX1 [Visual System Homeobox Gene 1], COL6A1 [Collagen, Type VI, Alpha-1], MMP9 [Matrix Metalloproteinase 9], KRT3 [Keratin 3]), and two putative loci, 3p14-q13 and 15q22.33-24) was undertaken using polymorphic markers, and haplotypes constructed. Multipoint linkage analysis was performed to generate LOD scores and produce LOD plots across the candidate intervals. RESULTS: No pathogenic sequence variations were detected in TGFBI or ZEB1 of the proband nor on the Asper Corneal Dystrophy gene chip (302 mutations in 12 genes). Multipoint linkage analysis of 11 known corneal genes and loci generated negative LOD plots and was able to exclude all genes tested including PIP5K3. CONCLUSIONS: Exclusion of linkage to candidate corneal loci combined with an absence of pathogenic mutations in known corneal genes in this pedigree suggest a different genetic causative mechanism in this dystrophy than the previously documented corneal genes. This unique phenotype of an anterior membrane dystrophy may therefore provide an opportunity to identify a new gene responsible for corneal disease.

UV damage of the anterior ocular surface - microstructural evidence by in vivo confocal microscopy.

PURPOSE: To evaluate and describe the microstructural changes at the ocular surface in response to habitual ocular sun exposure, correlate them with the UV protection habits and follow their dynamics using in vivo confocal microscopy(ICM). METHODS: For a period of minimum 4 months 200 subjects (400 eyes), aged 28 ±â€¯7.3 years, were recruited with the agreement that they will spend their summer exclusively in the region of the Black Sea coast at 43 °N latitude and will be examined before and after the summer. All subjects filled in a questionnaire about habitual UV protection and were examined clinically and by ICM. RESULTS: Questionnaire results demonstrated that 83.5% (167 participants) of the subjects considered the sun dangerous for their eyes, but 78% (156 subjects) believed that there is danger exclusively during the summer period. Although no clinical changes were detected, microstructural analysis of the cornea demonstrated statistically significant (p = 0.021) decrease of the basal epithelial density - from 6167 ±â€¯151 cells/mm2 before to 5829 ±â€¯168 cells/mm2 after the summer period. Microstructural assessment of the conjunctiva demonstrated characteristic cystic lesions with dark centres and bright borders encountered in only 25 eyes(6%) before, and affecting 118 eyes(29.5%) after the summer. The total area of the cysts after the summer increased fivefold. Spearman analysis proved negative correlation between sun protection habits and number of cysts. CONCLUSION: Summer sun exposure for one season leads to clinically undetectable, microstructural changes affecting the cornea, bulbar and palpebral conjunctiva with transient, but possibly cumulative nature.

In vivo confocal microstructural analysis of corneas presenting Kayser-Fleischer rings in patients with Wilson's disease.

PURPOSE: To evaluate microstructural differences between corneas with and without Kayser-Fleischer rings in age-matched subjects with Wilson's disease with neurological symptoms, using confocal laser scanning microscopy. METHODS: The study included 12 subjects with Wilson's disease with neurological symptoms. Twelve corneas presented clinically with classic Kayser-Fleischer rings, visible on slit lamp examination; the other 12 served as controls. The subjects underwent a comprehensive clinical examination. Microstructural analysis using confocal laser scanning microscopy evaluated increased corneal thickness, decreased number of cells, increased debris or specific deposits, and unusual microstructures. RESULTS: Clinically, the subjects with Kayser-Fleischer rings had similar corneal findings and normal intraocular pressure; two had typical sunflower cataracts and decreased visual acuity. The control eyes all presented normal visual acuity, intraocular pressure, and corneal appearance. The microstructural analysis demonstrated similar findings in all the affected corneas. Compared with the control corneas, there were fewer keratocytes in the anterior stroma (17.380 vs. 22.380/mm3). Round, "hollow" dark areas were observed between the keratocytes; these were universal and similar in appearance in all affected corneas and all cornea layers. In the peripheral posterior stroma, there were dust-like, bright, granular deposits that tended to increase in number and density toward Descemet's membrane, masking the peripheral endothelium. The control corneas presented a normal microstructure apart from dust-like granular deposits in the periphery. CONCLUSIONS: In vivo confocal microscopy is a useful tool for evaluating the corneal microstructure when a Kayser-Fleischer ring is clinically present. The ring consists of granular, bright particles that increase in density toward Descemet's membrane, and is associated with a decreased number of keratocytes and peculiar dark, round areas in all stromal layers, probably a sign of corneal damage. When the ring is not visible in subjects with Wilson's disease, changes to the corneal microstructure are insignificant.

Microstructural evaluation of the mucin balls and their relations to the corneal surface-Insights by in vivo confocal microscopy.

PURPOSE: The purpose of the current study was to observe and correlate the characteristics of mucin balls to the ocular surface properties, and furthermore, to report the effect of different mucin balls size and number on structural alteration of the anterior cornea. METHODS: The study included, two groups of patients fitted with one-month continuous, extended wear lenses for therapeutic (group 1) and optical (group 2) purposes; the later serving as a control group. Group 1 was comprised of patients with recurrent erosion syndrome, while group 2 included subjects with mild myopia and voluntary use of continuous wear lenses. The examination was performed when mucin balls were encountered during a routine visit. Clinical examination was reinforced with laser scanning in vivo confocal microscopy, which provided microstructural observations. The appearance and size of the mucin balls were described and measured at two independent time points. Qualitative analysis included shape (round, elliptical and irregular) and reflectivity (bright, homogenous and dark, heterogonous). RESULTS: Clinically 1460 mucin balls were encountered (822 in group 1 and 638 in group 2). The number of mucin balls analyzed by in vivo confocal microscopy was 820. Diversity was higher in group 1. The mucin balls of group 2, were more uniform - rounded in shape 81,2% and regular in reflectivity 98%. Qualitative analysis revealed a negative correlation between the size of the balls and impact on the basal epithelium morphology and also "activation" of the anterior stroma in adjacent areas. CONCLUSIONS: Mucin balls affect corneal surface including both epithelia disintegration as well as keratocyte "activation". The main predisposing factor for mucin ball formation appear to be the corneal surface irregularity. As structural alterations of the cornea are transient, mucin balls might be beneficial for corneal restoration due to mechanical and/or biochemical stimulation. In vivo, confocal microscopy is an innovative tool for evaluating mucin balls in their diversity and dynamics.

Imaging the microstructural abnormalities of meesmann corneal dystrophy by in vivo confocal microscopy.

PURPOSE: To delineate the microstructural features of Meesmann corneal dystrophy using in vivo confocal microscopy. METHOD: Three subjects with clinically diagnosed Meesmann corneal dystrophy were examined by slit-lamp biomicroscopy and slit-scanning in vivo confocal microscopy. RESULTS: On slit-lamp biomicroscopy, all subjects demonstrated large bilateral multiple epithelial cystic lesions extending to the midperiphery. On in vivo confocal microscopy, these lesions appeared as hyporeflective areas in the basal epithelial layer. The majority were circular, oval or teardrop shaped and ranged between 48 mum and 145 mum in diameter. Large elongated intraepithelial clefts were also seen. Reflective spots were visible within most of the lesions and these may represent the fibrillogranular material (termed peculiar substance) and tonofilament bundles observed in electron microscopy studies. An additional finding was the fragmented appearance of the subbasal nerve plexus. CONCLUSION: We present the first case series of Meesmann corneal dystrophy imaged by in vivo confocal microscopy and describe the associated microstructural features. Delineation of these features facilitates the use of the confocal microscope to aid diagnosis and management of corneal dystrophies.

In vivo confocal microscopy of posterior polymorphous dystrophy.

PURPOSE: This study was designed to delineate the morphologic features of posterior polymorphous dystrophy (PPD) using in vivo confocal microscopy. METHODS: Six patients with clinically diagnosed PPD were examined by slit-lamp biomicroscopy, Orbscan II slit-scanning elevation topography, and in vivo confocal microscopy. RESULTS: Endothelial cell densities ranged from 613 to 3,405 cells/mm and endothelial polymegathism was noted in all cases, whereas endothelial pleomorphism was not a prominent feature. Three cases exhibited bright endothelial nuclei. A variety of abnormal curvilinear and vesicular abnormalities were imaged by in vivo confocal microscopy, with lesions ranging between 6 and 159 microm in diameter. Abnormal endothelial cells were visible within some of these lesions. Six cases showed hyperreflectivity at the level of Descemet's membrane around the lesions. Deep stromal keratocytes appeared to aggregate around, or were compressed by, the endothelial lesions in one case. CONCLUSIONS: We report the largest case series of PPD imaged by in vivo confocal microscopy. The ability of in vivo confocal microscopy to assess the living cornea over time enables monitoring of disease progression and thus the potential to identify and correlate development of, or changes in, microstructural features. As more data become available, these analyses may enable the formulation of prognostic and diagnostic criteria.

The Auckland cataract study: co-morbidity, surgical techniques, and clinical outcomes in a public hospital service.

AIM: To prospectively assess cataract surgery in a major New Zealand public hospital by defining presenting clinical parameters and surgical and clinical outcomes in a cohort of subjects just below threshold for treatment, based upon a points based prioritisation system. METHODS: The prospective observational study comprised 488 eyes of 480 subjects undergoing consecutive cataract operations at Auckland Hospital. All subjects underwent extensive ophthalmic examination before and after surgery. Details of the surgical procedure, including any intraoperative difficulties or complications, were documented. Postoperative review was performed at 1 day and 4 weeks after surgery. Demographic data, clinical outcomes, and adverse events were correlated by an independent assessor. RESULTS: The mean age at surgery was 74.9 (SD 9.6) years with a female predominance (62%). Significant systemic disease affected 80% of subjects, with 20% of the overall cohort exhibiting diabetes mellitus. 26% of eyes exhibited coexisting ocular disease and in 7.6% this affected best spectacle corrected visual acuity (BSCVA). A mean spherical equivalent of -0.49 (1.03) D and mean BSCVA of 0.9 (0.6) log MAR units (Snellen equivalent approximately 6/48) was noted preoperatively. Local anaesthesia was employed in 99.8% of subjects (94.9% sub-Tenon's). The majority of procedures (97.3%) were small incision phacoemulsification with foldable lens implant. Complications included: 4.9% posterior capsule tears, 3.8% cystoid macular oedema, and one case (0.2%) of endophthalmitis. Mean BSCVA after surgery was 0.1 (0.2) log MAR units (6/7.5 Snellen equivalent), with a mean spherical equivalent of -0.46 (0.89) D, and was 6/12 or better in 88% of all eyes. A drop in BSCVA, thought to be directly attributable to the surgical intervention, was recorded in a small percentage of eyes (1.5%) after surgery. CONCLUSION: This study provides a representative assessment of the management of cataract in the New Zealand public hospital system. A predominantly elderly, female population, frequently exhibiting significant systemic illness and coexisting ocular disease, relatively advanced cataracts, and poor BSCVA, presented for cataract surgery. The majority of subjects underwent small incision, phacoemulsification, day case surgery. While almost 90% achieved at least 6/12 BSCVA post-surgery, approximately 5% sustained an adverse intraoperative event and 1.5% of eyes exhibited a reduction in BSCVA postoperatively.

Analyzing small-incision cataract surgery by Orbscan II fourth-dimensional pachymetry mapping.

PURPOSE: To assess the changes in pachymetry after routine corneal and scleral tunnel phacoemulsification. SETTING: Discipline of Ophthalmology, University of Auckland, Auckland, New Zealand. METHOD: This prospective study comprised 174 eyes of 174 consecutive patients having uneventful, small-incision, sutureless, phacoemulsification cataract surgery; 124 patients had a clear corneal incision and 50, a superior scleral tunnel incision. Difference pachymetry maps were derived from Orbscan II elevation topography data obtained before and 4 weeks after surgery. Corneal thickness changes at 12 midperipheral areas located in 12 meridians were derived from difference (subtraction) maps. The mean corneal thickness within a single area corresponding to the center of the surgical incision was compared to the mean pachymetry readings of all 12 midperipheral measurements. RESULTS: The overall mean midperipheral corneal thickness (12 samples per cornea) increased by a mean of 5.89 microm +/- 16.09 (SD) in the clear corneal incision group and 6.89 +/- 14.50 microm in the scleral tunnel group. The mean central corneal thickness increased by 7.28 +/- 20.98 microm and 7.74 +/- 21.34 microm, respectively. The corneal thickness in the meridian closest to the incision was significantly higher than the mean value of the 12 meridians measured in both groups, with means of 14.95 +/- 26.86 microm in the clear corneal group (P =.001) and 16.22 +/- 21.23 microm in the scleral tunnel group (P =.002). There were no statistically significant postoperative differences in the central, midperipheral, or incision-site corneal thickness measurements between the 2 surgical techniques (P =.77). CONCLUSIONS: Time-dependent (fourth-dimensional) pachymetry subtraction maps are useful for following corneal dynamics over time. This study found that small-incision phacoemulsification techniques--scleral and corneal tunnel--had a minor but similar effect on corneal thickness 4 weeks after surgery.

In vivo confocal microstructural analysis and surgical management of Brown-Mclean syndrome associated with spontaneous crystalline lens luxation.

We report 3 members of an extended family who presented with bilateral peripheral corneal edema consistent with Brown-McLean syndrome. On clinical examination, all eyes demonstrated normal central corneas and marked peripheral edema. In vivo confocal microscopy of the peripheral cornea highlighted similar observations in the 6 eyes including endothelial pigmentation, masked stromal structure due to edema, prominent nerves, and localized basal epithelial edema. In the central cornea, in vivo confocal microscopic observations highlighted large cellular structures with prominent nuclei in groups consisting of several cells of similar appearance. In vivo confocal microscopy may enhance the diagnosis of Brown-McLean syndrome and may be used for dynamic evaluation and postoperative follow-up of the structural corneal changes.

Keratoglobus and posterior subcapsular cataract: surgical considerations and in vivo microstructural analysis.

We report sporadic, bilateral keratoglobus associated with posterior subcapsular cataract in a 43-year-old man. Slitlamp biomicroscopy showed symmetric arcus senilis-like deposits, a polygonal appearance resembling crocodile shagreen, an unusual endothelial appearance, and posterior subcapsular cataract. Orbscan II pachymetry maps (Bausch & Lomb) demonstrated bilateral diffuse corneal thinning (359.53 microm +/- 21.15 [SD] in the right eye and 379.61 +/- 11.49 microm in the left eye). These thickness values were confirmed by ultrasound pachymetry. In vivo confocal microscopy showed multiple criss-crossing dark lines and no identifiable cellular elements within the stroma. There were mild to moderate, guttata-like endothelial changes surrounded by pleomorphic cells. Phacoemulsification was performed in the left eye after careful consideration of the presenting features and modification of the surgical technique. Minimal structural alteration was observed during microstructural analysis 7 months after surgery. The endothelial morphology postoperatively was similar to that at baseline.

In vivo microstructural analysis of the cornea in Scheie's syndrome.

PURPOSE: To analyze clinical and in vivo microstructural characteristics of both corneas of a 13-year-old male subject with Scheie's syndrome and compare the observations with the pathologic reports in the literature. METHODS: Standard clinical examination and real-time, slit-scanning in vivo confocal microscopy were performed and repeated after 1 year. RESULTS: In vivo confocal microscopy images at all cellular layers demonstrated brighter intercellular spaces than those of normal corneas. Cicatrization of the anterior stroma was identified, and the keratocytes of the middle and posterior stroma exhibited markedly altered morphology, often round or elliptical in shape, and with clearly demarcated, hyporeflective centers. The nerve fibers of the subbasal plexus were somewhat more irregular and difficult to distinguish, possibly due to underlying fibrosis. CONCLUSIONS: The potential of in vivo confocal microscopy to highlight microstructural alterations of the intact human cornea and evaluate such changes over time might reduce reliance on histopathologic investigations in such conditions and contribute to the ophthalmic management of the mucopolysaccharidoses in the future.

In vivo confocal microstructural analysis of corneas presenting Kayser-Fleischer rings in patients with Wilson's disease / Análise microestrutural confocal in vivo de córneas apresentando anel de Kayser-Fleischer em pacientes com doença de Wilson

ABSTRACT Purpose: To evaluate microstructural differences between corneas with and without Kayser-Fleischer rings in age-matched subjects with Wilson's disease with neurological symptoms, using confocal laser scanning microscopy. Methods: The study included 12 subjects with Wilson's disease with neurological symptoms. Twelve corneas presented clinically with classic Kayser-Fleischer rings, visible on slit lamp examination; the other 12 served as controls. The subjects underwent a comprehensive clinical examination. Microstructural analysis using confocal laser scanning microscopy evaluated increased corneal thickness, decreased number of cells, increased debris or specific deposits, and unusual microstructures. Results: Clinically, the subjects with Kayser-Fleischer rings had similar corneal findings and normal intraocular pressure; two had typical sunflower cataracts and decreased visual acuity. The control eyes all presented normal visual acuity, intraocular pressure, and corneal appearance. The microstructural analysis demonstrated similar findings in all the affected corneas. Compared with the control corneas, there were fewer keratocytes in the anterior stroma (17.380 vs. 22.380/mm3). Round, "hollow" dark areas were observed between the keratocytes; these were universal and similar in appearance in all affected corneas and all cornea layers. In the peripheral posterior stroma, there were dust-like, bright, granular deposits that tended to increase in number and density toward Descemet's membrane, masking the peripheral endothelium. The control corneas presented a normal microstructure apart from dust-like granular deposits in the periphery. Conclusions: In vivo confocal microscopy is a useful tool for evaluating the corneal microstructure when a Kayser-Fleischer ring is clinically present. The ring consists of granular, bright particles that increase in density toward Descemet's membrane, and is associated with a decreased number of keratocytes and peculiar dark, round areas in all stromal layers, probably a sign of corneal damage. When the ring is not visible in subjects with Wilson's disease, changes to the corneal microstructure are insignificant.

RESUMO Objetivo: Avaliar, ao nível microestrutural, através de microscopia confocal in vivo a lazer, 12 córneas com anel de Kayser-Fleischer visível ao exame da lâmpada de fenda e compará-las com 12 córneas clinicamente normais de indivíduos com idades correspondentes aos pacientes com doença de Wilson e sintomas neurológicos. Métodos: O estudo incluiu 12 indivíduos com doença de Wilson e sintomas neurológicos (24 córneas). Doze córneas apresentavam clinicamente o anel clássico de Kayser-Fleischer e as outras 12 serviram como controle. Todos os pacientes foram submetidos a um exame clínico abrangente e a uma análise microestrutural subsequente utilizando microscopia confocal in vivo de varredura a laser. Os principais resultados observados foram: aumento da espessura da córnea, diminuição do número de células, aumento de resíduos/depósitos específicos e microestrutura atípica. Resultados: Clinicamente, todos os indivíduos com anel de Kayser-Fleischer (12 olhos) apresentaram achados similares da córnea e pressão intraocular normal. Dois indivíduos também apresentaram uma catarata de girassol típica e diminuição da acuidade visual. Todos os olhos do grupo controle apresentaram acuidade visual, pressão intraocular e aparência corneana normais. A microscopia confocal in vivo com varredura a laser revelou achados semelhantes em todas as córneas afetadas. O número de ceratócitos no estroma anterior era menor, 17.380/mm3 (22.380/mm3 no grupo controle), e entre eles foram identificadas áreas escuras arredondadas "vazias". Essas zonas escuras eram generalizadas e similares em todas as córneas examinadas e em todas as camadas da córnea. No estroma posterior periférico, havia presença de depósitos granulares brilhantes e com aparência de pó que tendiam a aumentar em número e densidade no sentido da membrana de Descemet, mascarando o endotélio periférico. As córneas controle apresentaram estrutura normal, com exceção de depósitos granulares com aparência de pó na periferia. Conclusões: A microscopia confocal in vivo é uma ferramenta útil para a avaliação da microestrutura da córnea quando o anel de Kayser-Fleischer está clinicamente presente. O anel é constituído de partículas granulares brilhantes com densidade aumentada no sentido da membrana de Descemet. Sua presença está associada com uma diminuição do número de ceratócitos e com áreas circulares escuras "peculiares" em todas as camadas estromais, que representam, provavelmente, um sinal de dano da córnea. Quando o anel não está clinicamente visível, a estrutura da córnea in vivo encontra-se insignificantemente alterada.

Improved corneal wound healing through modulation of gap junction communication using connexin43-specific antisense oligodeoxynucleotides.

PURPOSE: Gap junctions play a major role in corneal wound healing. This study used reproducible models of corneal wound healing to evaluate the effect of a gap junction channel modulator, connexin43 (Cx43) antisense oligodeoxynucleotides (AsODN), on corneal healing dynamics. METHODS: A mechanical scrape wound model was used to evaluate Cx43 AsODN penetration and initial wound reepithelialization 12 hours postsurgery. Thereafter, detailed analyses of corneal edema, inflammation, and healing were performed in an excimer laser surface ablation model. In vivo confocal microscopy determined clinical parameters (edema, haze) and cellular changes (stromal hypercellularity, reepithelialization), whereas histology and immunohistochemistry were used to quantify stromal edema, inflammation, and reepithelialization. RESULTS: Cx43 AsODN penetrated through the hydrophilic stroma where the epithelium had been removed and accumulated in the basal epithelium close to the wound edge. Twelve hours after scrape wounding, Cx43 AsODN-treated eyes showed a significant reduction in wound area compared with the vehicle alone (1.59±0.37 and 2.29±0.58 mm2, respectively, P<0.01). After excimer laser ablation, stromal edema and inflammation were reduced, with endothelial structures being clearly visible, and reepithelialization rates were again increased in Cx43 AsODN-treated eyes. Histologic analysis confirmed reduced edema in the central wound site and at the periphery of treated corneas (P<0.05), whereas immunohistochemistry showed lower Cx43 levels (P<0.05), reduced myofibroblast activation, and improved epithelial basal lamina deposition in antisense-treated wounds (P<0.01). CONCLUSIONS: Application of Cx43 AsODN to the cornea reduces stromal edema and inflammation, promoting faster wound closure and a more uniform repair of the epithelial basal lamina after laser ablation.