Primary cysts of the iris pigment epithelium. Clinical features and natural course in 234 patients

Objective: To describe the clinical characteristics, natural course, and complications of a large group of patients with primary iris pigment epithelium (IPE) cysts. Design: Observational case series. Participants: Two hundred thirty-four patients with primary IPE cysts participated. Results: Primary IPE cysts were classified as central in 6 patients (3%), midzonal in 50 patients (21%), peripheral in 170 patients (73%), and dislodged in 8 patients (3%). Central (pupillary) IPE cysts were found only in males, peripheral IPE cysts were found most often in females (69%), and no gender predilection was detected for midzonal and dislodged IPE cysts. Central and peripheral IPE cysts occurred in young patients (mean age, 20 and 33 years, respectively), whereas midzonal and dislodged IPE cysts were seen in slightly older patients (mean age, 52 and 45 years, respectively). Central IPE cysts were visible when the pupil was not dilated and appeared most often as a round or collapsed brown lesion arising from the pupillary margin, most commonly superonasally. Midzonal IPE cysts were brown and fusiform, best visualized after pupillary dilation. Peripheral IPE cysts produced a characteristic bulging in the iris stroma near the iris root, but they were directly visible in only 78% of cases. After wide dilation and patient and slit-lamp positioning, they appeared as a round clear lesion behind the iris, most often in the inferotemporal quadrant. Finally, dislodged IPE cysts appeared as a brown oval lesion, free floating in the anterior chamber (12%) or in the vitreous (12%), or fixed in the anterior chamber angle (75%). One hundred twenty-four patients (53%) were followed for a mean of 35 months (range, 3 months-19 years). In these patients, complications associated with IPE cysts included lens subluxation in one case (1%), iritis in one case (1%), focal cataract in two cases (2%), glaucoma in two cases (2%), and corneal touch in five cases (4%). Conclusion: Primary IPE cysts have characteristic clinical features that serve to differentiate them from intraocular malignancies. Most cysts have a benign clinical course, and treatment is rarely necessary.

Indications for penetrating keratoplasty and associated procedures, 1989-1995

Purpose. To identify changing trends in indications for penetrating keratoplasty and associated surgical procedures. Methods. Review of charts from all patients who underwent penetrating keratoplasty at Wills Eye Hospital from January 1, 1989 through December 31, 1995. Results. A total of 2,442 corneal transplants were performed in 2,186 patients. The leading indication for penetrating keratoplasty was pseudophakic corneal edema, accounting for 634 cases (26.0%); 54.7% of them were associated with anterior chamber intraocular lenses, 36.4% with posterior chamber intraocular lenses, and 3.1% with iris-fixated intraocular lenses. Regraft (17.8%), Fuchs' dystrophy (15.7%), and keratoconus (13.2%) followed pseudophakic corneal edema in frequency. Cataract extraction, with or without intraocular lens implantation, was combined with penetrating keratoplasty in 439 cases of 1,264 phakic eyes (34.7%). Intraocular lens exchange was performed in 285 of the 634 cases of pseudophakic cornea edema (44.9%). Conclusion. Pseudophakic corneal edema was the leading indication for penetrating keratoplasty, with an increasing number of cases associated with posterior chamber intraocular lenses during the study period (p = 0.001). The number of regrafts steadily increased between 1989 and 1995 (p = 0.001), being the second most common indication for corneal transplantation since 1992.

Contact lens use after contact lens-associated infectious ulcers

Purpose: The purpose of this study was to evaluate the outcome of patients with healed moderate to severe contact lens-associated corneal infectious ulcers who were re-fit with contact lenses. Methods: We retrospectively studied patients who were fit with contact lenses on our service and who had had moderate to severe corneal infectious ulcers associated with previous contact lens use. Six patients were included in the study. Results: Gas permeable contact lenses were fit in five patients, and a soft contact lens was fit in one patient. Successful fit was achieved in all cases and visual acuities were equal to or better than 20/30 in all patients. No significant complications were observed after a mean follow-up of 23 months (range, 6-45 months). Conclusion: In this small series of patients with a history of moderate to severe contact-lens related infectious keratitis, no complications were observed after contact lenses were refit. Contact lens wear in patients with a history of infectious keratitis may be safe and useful in order to achieve visual rehabilitation.

Surveillance for ocular hypertension: An evidence synthesis and economic evaluation

OBJECTIVES: To determine effective and efficient monitoring criteria for ocular hypertension [raised intraocular pressure (IOP)] through (i) identification and validation of glaucoma risk prediction models; and (ii) development of models to determine optimal surveillance pathways.

DESIGN: A discrete event simulation economic modelling evaluation. Data from systematic reviews of risk prediction models and agreement between tonometers, secondary analyses of existing datasets (to validate identified risk models and determine optimal monitoring criteria) and public preferences were used to structure and populate the economic model.

SETTING: Primary and secondary care.

PARTICIPANTS: Adults with ocular hypertension (IOP > 21 mmHg) and the public (surveillance preferences).

INTERVENTIONS: We compared five pathways: two based on National Institute for Health and Clinical Excellence (NICE) guidelines with monitoring interval and treatment depending on initial risk stratification, 'NICE intensive' (4-monthly to annual monitoring) and 'NICE conservative' (6-monthly to biennial monitoring); two pathways, differing in location (hospital and community), with monitoring biennially and treatment initiated for a ≥ 6% 5-year glaucoma risk; and a 'treat all' pathway involving treatment with a prostaglandin analogue if IOP > 21 mmHg and IOP measured annually in the community.

MAIN OUTCOME MEASURES: Glaucoma cases detected; tonometer agreement; public preferences; costs; willingness to pay and quality-adjusted life-years (QALYs).

RESULTS: The best available glaucoma risk prediction model estimated the 5-year risk based on age and ocular predictors (IOP, central corneal thickness, optic nerve damage and index of visual field status). Taking the average of two IOP readings, by tonometry, true change was detected at two years. Sizeable measurement variability was noted between tonometers. There was a general public preference for monitoring; good communication and understanding of the process predicted service value. 'Treat all' was the least costly and 'NICE intensive' the most costly pathway. Biennial monitoring reduced the number of cases of glaucoma conversion compared with a 'treat all' pathway and provided more QALYs, but the incremental cost-effectiveness ratio (ICER) was considerably more than £30,000. The 'NICE intensive' pathway also avoided glaucoma conversion, but NICE-based pathways were either dominated (more costly and less effective) by biennial hospital monitoring or had a ICERs > £30,000. Results were not sensitive to the risk threshold for initiating surveillance but were sensitive to the risk threshold for initiating treatment, NHS costs and treatment adherence.

LIMITATIONS: Optimal monitoring intervals were based on IOP data. There were insufficient data to determine the optimal frequency of measurement of the visual field or optic nerve head for identification of glaucoma. The economic modelling took a 20-year time horizon which may be insufficient to capture long-term benefits. Sensitivity analyses may not fully capture the uncertainty surrounding parameter estimates.

CONCLUSIONS: For confirmed ocular hypertension, findings suggest that there is no clear benefit from intensive monitoring. Consideration of the patient experience is important. A cohort study is recommended to provide data to refine the glaucoma risk prediction model, determine the optimum type and frequency of serial glaucoma tests and estimate costs and patient preferences for monitoring and treatment.

FUNDING: The National Institute for Health Research Health Technology Assessment Programme.

Simultaneous use of mitomycin-C with Baerveldt implantation

BACKGROUND AND OBJECTIVE: To evaluate the outcome of Baerveldt implantation with adjunctive mitomycin-C in cases of complicated glaucoma. PATIENTS AND METHODS: The authors reviewed the charts of all patients who had undergone Baerveldt implantation with mitomycin-C between January 1993 and March 1995. Success was defined before data collection as an intraocular pressure (IOP) between 5 and 21 mm Hg, with or without medications. The success rate was calculated using the Kaplan-Meier actuarial method. RESULTS: Twenty-nine patients were identified. The mean preoperative IOP was 33.6 mm Hg, with an average of 2.0 antiglaucoma medications. The probability of success at 6 and 12 months for patients who received mitomycin-C during Baerveldt implantation was 82.4% and 73.3%, respectively. Choroidal effusion with a flat anterior chamber (10.3%), corneal edema (6.8%), and conjunctival erosion (6.8%) were the most frequent complications. CONCLUSION: In this retrospective series of complicated glaucoma, the implantation of a Baerveldt drainage device with adjunctive mitomycin-C had a satisfactory outcome. The complications encountered and the clinical efficacy were comparable to those of previously reported series in which mitomycin-C was not used.

Horizontal Descemet's membrane break due to birth trauma

We report an unusual case of horizontal corneal Descemet's membrane break due to birth trauma. The patient had a difficult birth with trauma to her right eye and poor vision. However unlike the reports in literature, which describe these breaks to have a characteristic vertical or vertically oblique orientation in birth trauma, the breaks in our patient were horizontal. No other cause was found for these Descemet's breaks.

Surgical technique:Complex glaucoma case requiring molteno drainage tube extension

A 42-year-old man has been under long-term follow-up since he was a child for congenital glaucoma and buphthalmos in both eyes. His left eye best corrected visual acuity (BCVA) was counting fingers, due to end-stage glaucoma. He was on maximal medical therapy with an intraocular pressure (IOP) maintained at mid to low twenties. His right eye, the only seeing eye, had a BCVA of 6/9. This eye had undergone multiple glaucoma laser and surgical procedures, including an initial first Molteno drainage device inserted superonasally that failed in April 2003 due to fibrotic membrane over the tube opening. As a result, he subsequently had a second Molteno drainage device inserted inferotemporally. To further maximize his vision he had an uncomplicated cataract extraction and intraocular lens implant in December 2004, after which he developed postoperative cystoid macular edema and corneal endothelial failure. He underwent a penetrating keratoplasty in the right eye thereafter in March 2007. After approximately a year, the second Molteno device developed drainage tube retraction, which was managed surgically to maintain optimum IOP in the right eye. His right eye vision to date is maintained at 6/12. © 2011 Mustafa and Azuara-Blanco.

Tono-Pen determination of intraocular pressure in patients with band keratopathy or glued cornea

Aims. To evaluate the intraocular pressure (IOP) measurements in patients with band keratopathy or glued corneas obtained from affected and non-affected areas. Methods. 15 patients with band keratopathy or glued corneas were prospectively recruited. When both eyes were affected, only the right eye was analysed. Tono-Pen readings of IOP were obtained sequentially from the affected and non-affected corneal surface. Additionally, Goldmann applanation tonometry was attempted. Results. Determination of IOP with the Tono-Pen was possible in all cases, while Goldmann tonometry was not performed in three patients because of severe corneal irregularities. The average of the Tono-Pen readings obtained from the affected cornea (34.8 (SD 14.0) mmHg) was consistently and significantly higher (p <0.001) than mean IOP obtained by the Tono-Pen from the non-affected area (14.8 (4.3) mmHg). The average of Goldmann tonometry readings (14.4 (6.1) mmHg) did not differ significantly from the Tono-Pen values obtained from the non-affected corneal area (p = 0.47) but was significantly lower than the Tono-Pen measurements obtained from the affected area (p <0.001) Conclusion. In patients with band keratopathy or glued corneas determination of IOP by Tono-Pen tonometry varies from affected to non-affected area. The Tono-Pen overestimates the level of IOP when it is applied to areas with band keratopathy or with glue.

Successful medical treatment of Acanthamoeba keratitis

Purpose: To describe the outcome of a series of Acanthamoeba keratitis treated with a similar regimen. Methods: All cases diagnosed with Acanthamoeba keratitis in a referral centre from June 1994 through June 1997 were included. Diagnosis of Acanthamoeba keratitis was based in clinical presentation and laboratory results. Positive laboratory identification of Acanthamoeba from corneal scraping or contact lens was required, unless the patient had very characteristic symptoms (severe pain) and signs of the infection, including perineural infiltrates. Initial intensive treatment included topical polyhexamethylene biguanide (PHMB) 0.02%, propamidine isothionate 0.1% and broad-spectrum antibiotics. The treatment was gradually tapered. After documented response to anti-acanthamoeba therapy, topical steroids were introduced; they were discontinued before cessation of the antiAcanthamoeba regimen. Results: Six males and four females, with a mean age of 30.0 ± 7.4 years were included in this study. All cases weared contact lenses. On presentation all cases had severe pain, and epitheliopathy was associated with stromal infiltrate in most (seven of ten) cases. Four patients had anterior uveitis. Perineural infiltrates were present in three cases and ring infiltrate in one patient. Anti-amoebic treatment was started 12.7 ± 7.2 days after beginning of symptoms. The clinical response to therapy was very satisfactory in all patients. Within two to three weeks all patients had remarkable lessening of pain and photophobia, and improvement of clinical signs. At two to three months, visual acuity had improved in all patients. Two patients required penetrating keratoplasty for visual rehabilitation. Conclusion: The use of PHMB and propamidine cured all cases of Acanthamoeba keratitis. Cautious introduction of steroids was associated with expedited resolution of inflammation and provided symptomatic relief.

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.

Ultrasound biomicroscopy in infantile glaucoma

Background: Glaucoma in infants has many causes. Evaluation of the anatomy of the anterior segment of eyes with infantile glaucoma may help to determine the pathogenesis of an infant's disease and influence therapeutic decisions. Methods: Eleven eyes of six infants with glaucoma were evaluated with ultrasound biomicroscopy (UBM) to evaluate the anatomic characteristics and relationships of the anterior segment structures. Results: The anterior chamber angle, iris, lens, ciliary body, and posterior chamber angle could be imaged in detail. Elongated and anteriorly placed ciliary processes were noted in all eight eyes with trabeculodysgenesis. There were no apparent anomalies in the trabecular meshwork, or anterior chamber. In three eyes with dense corneal opacities, ultrasound biomicroscopy showed severe anterior segment disorganization and thin central corneas with posterior corneal excavation. Conclusions: Ultrasound biomicroscopy is a useful non-invasive method for evaluating infants with glaucoma in cases with corneal opacities. This information can help in surgical planning for glaucoma management.

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 surgery for further 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.

A novel single base deletion in the LDLR gene (211delG):Effect on serum lipid profiles and the influence of other genetic polymorphisms in the ACE, APOE and APOB genes

A single base deletion (211delG) in the low density lipoprotein receptor (LDLR) gene was shown to cause familial hypercholesterolaemia (FH) in a large family from Northern Ireland. Twenty-four of 52 family members tested had this mutation, 13 of which were newly diagnosed. Mutation-positive individuals had significantly higher mean total-cholesterol (TC) and LDL-cholesterol (LDL-C) than those without 211delG. LDL-C was a more accurate indicator of disease status than TC, When TC levels alone were considered, in individuals over 16 years, a false negative rate (TC <7.5 mmol/l) of 40% was found; however, this fell to 13% based on inclusion of LDL-C levels. Individuals with coronary artery disease (CAD) had significantly higher TC levels than those without CAD and tended to have tendinous xanthomas (TX) and corneal arcus (CA). Genetic polymorphisms in the angiotensin converting enzyme (ACE) and apolipoprotein (ape) B genes did not appear to be associated with lipid levels or with the clinical severity of the disease; however, the apo E e4 allele did show a lipid-raising effect in individuals with the mutation.

Enrichment of pathogenic alleles in the brittle cornea gene, ZNF469, in keratoconus

Keratoconus, a common inherited ocular disorder resulting in progressive corneal thinning, is the leading indication for corneal transplantation in the developed world. Genome-wide association studies have identified common SNPs 100 kb upstream of ZNF469 strongly associated with corneal thickness. Homozygous mutations in ZNF469 and PR domain-containing protein 5 (PRDM5) genes result in brittle cornea syndrome (BCS) Types 1 and 2, respectively. BCS is an autosomal recessive generalized connective tissue disorder associated with extreme corneal thinning and a high risk of corneal rupture. Some individuals with heterozygous PRDM5 mutations demonstrate a carrier ocular phenotype, which includes a mildly reduced corneal thickness, keratoconus and blue sclera. We hypothesized that heterozygous variants in PRDM5 and ZNF469 predispose to the development of isolated keratoconus. We found a significant enrichment of potentially pathologic heterozygous alleles in ZNF469 associated with the development of keratoconus (P = 0.00102) resulting in a relative risk of 12.0. This enrichment of rare potentially pathogenic alleles in ZNF469 in 12.5% of keratoconus patients represents a significant mutational load and highlights ZNF469 as the most significant genetic factor responsible for keratoconus identified to date.

Capsulotomy worsens diabetic retinopathy in the Ins2Akitamice

Purpose: Cataract surgery increases the risk of developing diabetic retinopathy (DR) and accelerates the progression of pre-existing DR. Recent evidence suggests that cataract surgery elicits retinal pro-inflammatory gene expression, although the underlying pathogenic mechanisms remain ill-defined. In this study, we investigated the effect of capsulotomy on visual function, retinal immune cell activation and photoreceptor stress in the Ins2Akita mice, a mouse model of Type-1 diabetes. Methods: Male heterozygous Ins2Akita mice (2 months of hyperglycemia) and C57BL/6J age-matched siblings were used in this study. An incision (1mm) was made in the peripheral cornea and Capsulotomy was performed in the anterior lens capsule of the right eye. Control mice received corneal incision without capsulotomy in the right eye. The unoperated left eyes were used as internal controls. Forty days following surgery, retinal function was assessed by electroretinography (ERG). Neuronal retinal damage and microglial activation were assessed by imunohistochemistry. Results: The Ins2Akita mice receiving capsulotomy presented lower scotopic a-wave, b-wave and oscillatory potentials amplitudes compared to other experimental groups. Fundus images, SD-OCT and H&E staining did not show significant changes between different groups. Immunostaining of Iba-1 and CD68 revealed exacerbated microglial activation and giant cell immune cell infiltration in eyes receiving capsulotomy in Ins2Akita mice. This was accompanied by a disruption of cone photoreceptor outer segments and abnormal rhodopsin expression at the outer nuclear layer. Conclusions: Our results suggest that capsulotomy induces retinal microglial activation and worsens retinal neuropathy in diabetic eyes.