Augusto Azuara-Blanco

Amniotic membrane transplantation for ocular surface reconstruction.

AIMS To evaluate the efficacy of amniotic membrane transplantation (AMT) for ocular surface reconstruction. METHODS 10 consecutive patients who underwent AMT were included. The indications were: group A, cases with persistent epithelial defect after corneal abscess (n=1), radiation (n=1), or chemical burn (n=3); group B, cases with epithelial defect and severe stromal thinning and impending or recent perforation, due to chemical burn (two patients, three eyes) or corneal abscess (n=2); group C, to promote corneal epithelium healing and prevent scarring after symblepharon surgery with extensive corneo-conjunctival adhesion (n=1). Under sterile conditions amniotic membrane was prepared from a fresh placenta of a seronegative pregnant woman and stored at −70°C. This technique involved the use of amniotic membrane to cover the entire cornea and perilimbal area in groups A and B, and the epithelial defect only in group C. RESULTS The cornea healed satisfactorily in four of five patients in group A, but the epithelial defect recurred in one of these patients. After AMT three patients underwent limbal transplantation and one penetrating keratoplasty and cataract extraction. In group B amniotic membrane transplantation was not helpful, and all cases underwent an urgent tectonic corneal graft. Surgery successfully released the symblepharon, promoted epithelialisation and prevented adhesions in the case of group C. CONCLUSION AMT was effective to promote corneal healing in patients with persistent epithelial defect, and appeared to be helpful after surgery to release corneo-conjunctival adhesion. Most cases required further surgery for visual and ocular surface rehabilitation. Amniotic membrane used as a patch was not effective to prevent tectonic corneal graft in cases with severe stromal thinning and impending or recent perforation.

Amniotic membrane transplantation

In 1910 Davis was the first to report the use of fetal membranes as surgical material in skin transplantation.1Since then the use of amniotic membrane in surgery has been expanded.1-9 It is now utilised as a biological dressing for burned skin, skin wounds, and chronic ulcers of the leg,9-16 as an adjunctive tissue in surgical reconstruction of artificial vagina,9 17-19 and for repairing omphaloceles.9 20 It has also been used to prevent tissue adhesion in surgical procedures of the abdomen, head, and pelvis.9 21 22 In the 1940s several authors reported the beneficial role of amniotic membrane in treating a variety of ocular surface disorders.5-7 23 However, its use was abandoned for decades until recently, when it was reintroduced to ophthalmologists. Several studies have addressed this subject and the scope of the application of amniotic membrane transplantation (AMT) in the management of ocular surface disorders is ever increasing. Certain characteristics make the amniotic membrane ideally suited to its application in ocular surface reconstruction. It can be easily obtained and its availability is nearly unlimited. The tissue can be preserved at −80°C for several months, allowing sufficient time to plan surgery or consider a trial of other options. Amniotic membrane does not express HLA-A, B, or DR antigens and hence immunological rejection after its transplantation does not occur.24-26It is also believed to have antimicrobial properties, reducing the risks of postoperative infection.27 Antifibroblastic activity28-30 and cell migration/growth promoting activity31-33 have also been demonstrated with regard to the amniotic membrane. The purpose of this paper is to review the characteristics of amniotic membrane that make it potentially useful to treat ocular surface abnormalities and to discuss the current indications, the surgical technique, and the outcome of AMT. Mammalian embryos lie …

Dysfunctional Filtering Blebs

Guarded filtration surgery, is commonly used to control the intraocular pressure (IOP) in glaucomatous patients. Filtration surgery lowers the IOP by creating a fistula between the inner compartments of the eye and the subconjunctival space (i.e., filtering bleb). There are several options to improve the function of filtering blebs and to prevent their failure. However, improvement of IOP control after guarded filtration procedures is associated with a higher frequency of bleb-related complications. Early (e.g., bleb leak, excessive filtration, flat anterior chamber, filtration failure) and late (e.g., bleb leak, excessive filtration and hypotony, symptomatic blebs, bleb encapsulation, filtration failure, bleb infection) complications associated with filtering procedures should be managed adequately to prevent further problems. Techniques to improve the function of filtering blebs and to treat postoperative complications have progressed over the past decade.

Autologous limbal transplantation in patients with unilateral corneal stem cell deficiency

AIM To describe a surgical technique for autologous limbal stem cell transplantation and the outcome of a series of patients with unilateral stem cell deficiency. METHODS A report of six consecutive patients who underwent autologous limbal stem cell transplantation is presented. The primary diagnosis included alkali burn (n=3), conjunctival intraepithelial neoplasia (CIN) (n=1), recurrent pterygium (n=1), and contact lens induced keratopathy (n=1). The autologous transplanted tissue consisted of peripheral cornea, limbus, and conjunctiva obtained from the contralateral eye. Three of the above patients underwent penetrating keratoplasty in association with auto-limbal transplantation. A significant modification to established techniques was the close monitoring of conjunctival epithelial migration in the immediate postoperative period. If conjunctival epithelium threatened to migrate on to the corneal surface, it was mechanically removed at the slit lamp and prevented from crossing the limbus. This was required in three patients. RESULTS The mean follow up was 18.8 months. The outcome was satisfactory in all cases: a stable corneal surface was restored and there was a substantial improvement in vision and symptoms. One patient had a primary failure of the corneal allograft associated with glaucoma, and 6 months later developed a retinal detachment. No complications were noted in the donor eye with the exception of one patient who developed filamentary keratitis along the edge of the donor site. CONCLUSION Autologous limbal transplantation with corneal, limbal, and conjunctival carriers was found to be useful for ocular surface reconstruction, over a mid-term follow up, in patients with unilateral stem cell deficiency. Close monitoring of the migration of conjunctival epithelium in the immediate postoperative period, and preventing it from crossing the limbus, ensured that the corneal surface was re-epithelialised exclusively from epithelial cells derived from the transplanted limbal tissue. This approach should improve the success of this procedure.

Latanoprost for open-angle glaucoma (UKGTS): a randomised, multicentre, placebo-controlled trial

BACKGROUND Treatments for open-angle glaucoma aim to prevent vision loss through lowering of intraocular pressure, but to our knowledge no placebo-controlled trials have assessed visual function preservation, and the observation periods of previous (unmasked) trials have typically been at least 5 years. We assessed vision preservation in patients given latanoprost compared with those given placebo. METHODS In this randomised, triple-masked, placebo-controlled trial, we enrolled patients with newly diagnosed open-angle glaucoma at ten UK centres (tertiary referral centres, teaching hospitals, and district general hospitals). Eligible patients were randomly allocated (1:1) with a website-generated randomisation schedule, stratified by centre and with a permuted block design, to receive either latanoprost 0·005% (intervention group) or placebo (control group) eye drops. Drops were administered from identical bottles, once a day, to both eyes. The primary outcome was time to visual field deterioration within 24 months. Analyses were done in all individuals with follow-up data. The Data and Safety Monitoring Committee (DSMC) recommended stopping the trial on Jan 6, 2011 (last patient visit July, 2011), after an interim analysis, and suggested a change in primary outcome from the difference in proportions of patients with incident progression between groups to time to visual field deterioration within 24 months. This trial is registered, number ISRCTN96423140. FINDINGS We enrolled 516 individuals between Dec 1, 2006, and March 16, 2010. Baseline mean intraocular pressure was 19·6 mm Hg (SD 4·6) in 258 patients in the latanoprost group and 20·1 mm Hg (4·8) in 258 controls. At 24 months, mean reduction in intraocular pressure was 3·8 mm Hg (4·0) in 231 patients assessed in the latanoprost group and 0·9 mm Hg (3·8) in 230 patients assessed in the placebo group. Visual field preservation was significantly longer in the latanoprost group than in the placebo group: adjusted hazard ratio (HR) 0·44 (95% CI 0·28-0·69; p=0·0003). We noted 18 serious adverse events, none attributable to the study drug. INTERPRETATION This is the first randomised placebo-controlled trial to show preservation of the visual field with an intraocular-pressure-lowering drug in patients with open-angle glaucoma. The study design enabled significant differences in vision to be assessed in a relatively short observation period. FUNDING Pfizer, UK National Institute for Health Research Biomedical Research Centre.

Allo-limbal transplantation in patients with limbal stem cell deficiency

AIM To report the outcome of a series of patients with stem cell deficiency who underwent allo-limbal transplantation and to describe a technique for this procedure. METHODS Six consecutive patients underwent allo-limbal stem cell transplantation. The primary diagnosis included alkali burn (n=2), trachoma (n=1), chronic rosacea blepharitis and keratoconjunctivitis (n=1), aniridia (n=1), and Stevens–Johnson syndrome (n=1). The limbal rim consisted of peripheral cornea and perilimbal sclera. FK-506 was used postoperatively for immunosuppression. RESULTS The length of follow up ranged from 3 to 24 months (mean follow up 11.8 (SD 9.3) months). The outcome was considered satisfactory in five of six cases. The corneal surface was completely epithelialised within 2 weeks, and there was a substantial improvement in vision and symptoms. One patient had recurrent epithelial defects related to eyelid abnormalities. No side effects associated with systemic immunosuppression were noted. CONCLUSION Allo-limbal transplantation, with systemic immunosuppression with FK-506 is useful in reconstruction of the ocular surface with improvement in vision in patients with severe stem cell deficiency.

Incidence of glaucoma in patients with uveitis.

Purpose:To evaluate the incidence of glaucoma and elevation of intraocular pressure (IOP) in patients with inflammatory eye disease. Methods:Retrospective review of medical records of 391 consecutive patients with uveitis attending a uveitis clinic of an academic Department of Ophthalmology from January 1999 to August 2002. Demographic, ocular and systemic variables were recorded. The diagnosis and treatment of uveitis were recorded. Uveitis was classified according to standard anatomic, etiological and clinical criteria. “Glaucoma” was defined as elevated IOP (>21 mm Hg) or glaucomatous optic nerve damage requiring medical and/or surgical anti-glaucoma treatment. Kaplan-Maier analysis and log-rank tests were used to evaluate and compare the incidence of glaucoma. Results:The incidence of glaucoma as defined above at 3 and 12 months after acute uveitis was 7.6%. In patients with chronic uveitis (n = 337), the incidence of glaucoma at 1 and 5 years was 6.5% and 11.1%, respectively. There was no statistically significant difference in the incidence of glaucoma between different types of uveitis, idiopathic versus non-idiopathic, and among anterior, intermediate, posterior and panuveitis. Visual loss occurred more frequently in patients with glaucoma than in patients without glaucoma. Conclusion:In patients with chronic inflammatory eye disease, the presence of glaucoma was associated with an increasing risk of visual loss. The incidence of glaucoma increased with time and was similar among the different types of uveitis.

Clinical agreement among glaucoma experts in the detection of glaucomatous changes of the optic disk using simultaneous stereoscopic photographs.

PURPOSE To evaluate the clinical agreement in the detection of optic disk changes in patients with glaucoma using simultaneous stereophotographs. DESIGN Masked-observer variability study. METHODS Ten glaucoma specialists examined pairs of simultaneous stereophotographs of glaucomatous and control optic disks to determine whether there were changes compatible with progression of glaucomatous damage. RESULTS Intraobserver agreement had a kappa value ranging from 0.55 to 0.78. Interobserver agreement among the glaucoma specialists had a kappa value ranging from 0.34 to 0.68. CONCLUSIONS Clinical examination of stereophotographs to detect optic disk changes in glaucoma patients has limitations associated with suboptimal reproducibility.

Meta-analysis of randomised controlled trials comparing latanoprost with timolol in the treatment of patients with open angle glaucoma or ocular hypertension

AIM To evaluate the comparative efficacy and tolerance of latanoprost versus timolol through a meta-analysis of randomised controlled trials (RCTs). METHODS Systematic retrieval of RCTs of latanoprost versus timolol to allow pooling of results from head to head comparison studies. Quality of trials was assessed based on randomisation, masking, and withdrawal. Sensitivity analyses were used to estimate the effects of quality of study on outcomes. The data sources were Medline, Embase, Scientific Citation Index, Merck Glaucoma, and Pharmacia and Upjohn ophthalmology databases. There were 1256 patients with open angle glaucoma or ocular hypertension reported in 11 trials of latanoprost versus timolol. The main outcome measures were (i) percentage intraocular pressure (IOP) reduction for efficacy; (ii) relative risk, risk difference, and number needed to harm for side effects such as hyperaemia, conjunctivitis, increased pigmentation, hypotension, and bradycardia expressed as dichotomous outcomes; and (iii) reduction in systemic blood pressure and heart rate as side effects. RESULTS Both 0.005% latanoprost once daily and 0.5% timolol twice daily reduced IOP. The percentage reductions in IOP from baseline (mean (SE)) produced by latanoprost and timolol were 30.2 (2.3) and 26.9 (3.4) at 3 months. The difference in IOP reduction between the two treatments were 5.0 (95% confidence intervals 2.8, 7.3). However, latanoprost caused iris pigmentation in more patients than timolol (relative risk = 8.01, 95% confidence intervals 1.87, 34.30). The 2 year risk with latanoprost reached 18% (51/277). Hyperaemia was also more often observed with latanoprost (relative risk =2.20, 95% confidence intervals 1.33, 3.64). Timolol caused a significant reduction in heart rate of 4 beats/minute (95% confidence interval 2, 6). CONCLUSION This meta-analysis suggests that latanoprost is more effective than timolol in lowering IOP. However, it often causes iris pigmentation. While current evidence suggests that this pigmentation is benign, careful lifetime evaluation of patients is still justified.

Cannabinoids and glaucoma

Glaucoma is one of the leading causes of blindness in the world. In spite of the diverse therapeutic possibilities, new and better treatments for glaucoma are highly desirable. Cannabinoids effectively lower the intraocular pressure (IOP) and have neuroprotective actions. Thus, they could potentially be useful in the treatment of glaucoma. The purpose of this article is to provide the reader with an overview of the latest achievements in research into the potential use of cannabinoids for glaucoma.