Medically reversible limbal stem cell disease: clinical features and management strategies.

PURPOSE: To describe the clinical features and management strategies in patients whose limbal stem cell (LSC) disease reversed with medical therapy. DESIGN: Retrospective case series. PARTICIPANTS: Twenty-two eyes of 15 patients seen at 3 tertiary referral centers between 2007 and 2011 with 3 months or more of follow-up. METHODS: Medical records of patients with medically reversible LSC disease were reviewed. Demographic data, causes, location and duration of disease, and medical inventions were analyzed. MAIN OUTCOME MEASURES: Primary outcomes assessed included resolution of signs of LSC disease and improvement in visual acuity. RESULTS: Causes of the LSC disease included contact lens wear only (13 eyes), contact lens wear in the setting of ocular rosacea (3 eyes), benzalkonium chloride toxicity (2 eyes), and idiopathic (4 eyes). Ophthalmologic findings included loss of limbal architecture, a whorl-like epitheliopathy, or an opaque epithelium arising from the limbus with late fluorescein staining. The superior limbus was the most common site of involvement (95%). The corneal epithelial phenotype returned to normal with only conservative measures, including lubrication and discontinuing contact lens wear in 4 patients (4 eyes), whereas in 11 patients (18 eyes), additional interventions were required after at least 3 months of conservative therapy. Medical interventions included topical corticosteroids, topical cyclosporine, topical vitamin A, oral doxycycline, punctal occlusion, or a combination thereof. All eyes achieved a stable ocular surface over a mean follow-up of 15 months (range, 4-60 months). Visual acuity improved from a mean of 20/42 to 20/26 (P < 0.0184). CONCLUSIONS: Disturbances to the LSC function, niche, or both may be reversible with medical therapy. These cases, which represent a subset of patients with LSC deficiency, may be considered to have LSC niche dysfunction.

Exclusion of pathogenic promoter region variants and identification of novel nonsense mutations in the zinc finger E-box binding homeobox 1 gene in posterior polymorphous corneal dystrophy.

PURPOSE: To report the identification of five novel nonsense mutations in the zinc finger E-box binding homeobox 1 (ZEB1) gene and exclusion of promoter region mutations in individuals without ZEB1 coding region mutations in posterior polymorphous corneal dystrophy (PPCD). METHODS: Slit-lamp examination and DNA collection were performed for individuals diagnosed with PPCD and, when available, affected and unaffected family members. Genomic DNA prepared from peripheral blood leukocytes and buccal epithelial cells underwent PCR amplification and automated sequencing of the ZEB1 gene and 1 kb 5' of ZEB1, presumably containing the ZEB1 promoter region. RESULTS: Thirteen unrelated individuals with PPCD were identified, and genomic DNA was collected from each individual. ZEB1 mutations were identified in six of the 13 probands, five of which were novel: p.(Gly150Alafs*36; spontaneous), p.(His230Argfs*7), p.(Ser638Cysfs*5), p.(Glu1039Glyfs*6), and p.(Gln884Argfs*37). Screening of the ZEB1 promoter region in 31 probands with PPCD without a ZEB1 coding region mutation identified only two known single nucleotide polymorphisms (SNPs) whose frequency in the affected probands did not differ significantly from that in the general population. CONCLUSIONS: We report five novel frame-shift mutations, one confirmed as spontaneous, in the ZEB1 gene associated with PPCD, bringing the total number of reported pathogenic mutations to 24, and the percentage of PPCD associated with ZEB1 mutations to 32%. The absence of ZEB1 promoter region mutations in probands without a ZEB1 coding region mutation indicates that other genetic loci, such as the PPCD1 locus, are involved in the pathogenesis of PPCD.

Cryotherapy of sclerotomy sites for prevention of late post-vitrectomy diabetic hemorrhage: a randomized clinical trial.

BACKGROUND: To evaluate the role of cryotherapy of sclerotomy sites in prevention of late (after 4 weeks) post-vitrectomy diabetic hemorrhage. METHODS: In a prospective randomized double-masked clinical trial, a total of 124 eyes of 119 patients underwent pars plana vitrectomy for complications of proliferative diabetic retinopathy. At the end of vitrectomy, the eyes were randomly assigned to two groups. The case group received two cryotherapy spots at each sclerotomy site, whereas the eyes in the control group received no further intervention. Evaluations were repeated at months 1, 2, 4, and 6. The primary outcome measure was occurrence of vitreous hemorrhage after the first month and up to the sixth month. Ultrasound biomicroscopy (UBM) examination of the sclerotomy sites was performed concurrent with the occurrence of vitreous hemorrhage or at the last follow-up. RESULTS: Thirty-six eyes were excluded mostly because of early postoperative vitreous hemorrhage. Finally, the data of 42 eyes of the cases and 46 eyes of the controls were used for analysis. Late vitreous hemorrhage occurred in 17 out of 88 eyes (19.3%). This rate was significantly higher in the cases compared to the controls, 28.6% (12 eyes) versus 10.9% (five eyes) within 6 months (P = 0.036). There was no statistically significant difference in the UBM findings of the sclerotomy sites between the two groups. No relationship was noticed between morphologic patterns detected by UBM and occurrence of late vitreous hemorrhage. CONCLUSIONS: Cryotherapy of the sclerotomy sites at the end of the operation is not helpful for prevention of late post-vitrectomy diabetic hemorrhage, and it may even increase this risk.

Pupil dilation with intracameral lidocaine during phacoemulsification.

PURPOSE: To evaluate pupil dilation by an intracameral injection of nonpreserved lidocaine 1% during phacoemulsification cataract extraction and compare the results with those using conventional topical mydriatics. SETTING: Department of Ophthalmology, Rassoul Akram Hospital, Iran University of Medical Sciences, Tehran, Iran. METHODS: A prospective comparative case series study was conducted. The study included 57 patients who were given topical mydriatics (30 eyes) or intracameral lidocaine (27 eyes) to dilate the pupil for phacoemulsification and intraocular lens implantation. The topical group received 3 drops of cyclopentolate 1% and phenylephrine 5% given 5 minutes apart starting 60 minutes before surgery. The intracameral group received preservative-free lidocaine 1% (0.2 to 0.3 mL) injected just before the procedure began. No epinephrine was added to the irrigating solution. In both groups, the horizontal pupil diameter was measured before and after pupil dilation using the same caliper. Total surgical time, need for a mydriatic agent during the procedure, and subjective surgical performance were recorded. RESULTS: The mean age, sex, cataract density, baseline horizontal pupil diameter, and mean duration of the surgery were the same between the topical group and intracameral group. The mean pupil dilation was 4.52 mm +/- 0.08 (SD) in the intracameral group and 4.06 +/- 0.09 mm in the topical group; the difference between groups was statistically significant (P = .001). There was no significant difference between groups in the overall subjective surgical performance (P = .74). No patient in the intracameral group and 2 patients in the topical group required an intracameral mydriatic injection. CONCLUSION: During phacoemulsification, intracameral preservative-free lidocaine 1% provided rapid, effective mydriasis comparable that of topical mydriatics.

Cataract surgery for congenital cataract: endothelial cell characteristics, corneal thickness, and impact on intraocular pressure.

PURPOSE: To investigate whether central corneal thickness (CCT), endothelial cell characteristics, and intraocular pressure (IOP) are affected in patients with previous congenital cataract surgery and to focus on their clinical significance. METHODS: CCT and IOP measurements and specular microscopy were performed in 31 eyes of 17 cases of extracted congenital cataracts and 40 eyes of 20 age- and sex-matched participants as control group. The mean of three pachymetry measurements of the central cornea was taken as CCT. IOP was checked using an applanation tonometer. RESULTS: The mean corneal thickness of the eyes with extracted congenital cataract (632+/-45 microm) was significantly greater than that of the control eyes (546+/-33 microm; p<0.001). There was no significant difference in the corneal endothelial cell count, coefficient of variation (CV), and mean cell area (AVG) of endothelial cells between operated eyes and the control group. The mean measured IOP in the operated group (22.8+/-3.3 mm Hg) was significantly greater than IOP in controls (14.1+/-1.8 mm Hg, p<0.001). CONCLUSIONS: Although the corneas were clinically clear and there was no significant difference in endothelial characteristics of eyes with extracted congenital cataract and controls, central corneas of operated eyes were significantly thicker than those of controls. To differentiate the actual glaucoma from ocular hypertension in these patients, the central corneal thickness measurement should strongly be considered.

Presentation, diagnosis and management of limbal stem cell deficiency.

The human corneal surface epithelium is continuously repopulated by the limbal stem cells (LSCs). Limbal Stem Cell Deficiency (LSCD) can lead to corneal opacity and vascularization, with consequent visual impairment or blindness. Many acquired and congenital diseases can lead to LCSD by direct injury to the LSCs, destruction of LSC niche, or both. Based on the severity of the disease, LSCD can present with various symptoms and signs. Although LSCD can be detected clinically, laboratory tests are necessary to confirm the diagnosis and monitor the disease progression. This article concisely reviews the clinical presentation, techniques for diagnosis and management of LSCD.

Corneal keloid: report of natural history and outcome of surgical management in two cases.

PURPOSE: To report the natural history and the outcome after the surgical management of 2 cases of corneal keloids. METHODS: Two male patients, 21 and 24 years old, with a history of corneal opacity for 5 and 17 years, respectively, with no history of an ocular trauma were studied. RESULTS: The first patient initially underwent a superficial keratectomy (SK), after which the corneal opacification recurred. He subsequently underwent 2 SK procedures combined with phototherapeutic keratectomy and mitomycin C, followed by a femtosecond laser-assisted deep anterior lamellar keratoplasty. The second patient underwent a bilateral SK followed by a penetrating keratoplasty in the left eye with the rapid recurrence of the lesion. The patient subsequently underwent an implantation of a Boston type 1 keratoprosthesis in the right eye, with a favorable outcome. The histopathologic features of both excised corneal specimens were consistent with the diagnosis of a corneal keloid. CONCLUSIONS: Corneal keloids recur after SK and phototherapeutic keratectomy, indicating that keratoplasty procedures may be more effective than keratectomy procedures in their management. However, corneal keloids may recur even after a penetrating keratoplasty, in which case keratoprosthesis implantation represents a viable option for visual rehabilitation.

Surgical and visual outcomes of the type I Boston Keratoprosthesis for the management of aniridic fibrosis syndrome in congenital aniridia.

PURPOSE: To report the clinical features and surgical management of aniridic fibrosis syndrome using the type I Boston Keratoprosthesis (KPro). DESIGN: Interventional case series. METHODS: Retrospective chart review of 9 eyes in 9 patients with congenital aniridia that developed aniridic fibrosis syndrome. RESULTS: All patients had clinical diagnosis of congenital aniridia. Previously, all patients had undergone cataract surgery with posterior chamber intraocular lens (IOL) implantation and 7 patients had existing tube shunts. In all cases, fibrosis presented as progressive retrocorneal and retrolenticular membrane formation causing displacement of the IOL and secondary corneal decompensation. Two eyes had tractional folds in the retina with posterior extension of the membrane. The management included IOL explantation in 7 of 9 cases, removal of fibrosis with pars plana vitrectomy in all 9 patients, and implantation of a type I Boston KPro in all eyes. At a mean final follow-up of 26.1 months (range 6 to 48 months), vision remained improved in all patients. No patient had recurrence of the fibrotic membrane after KPro implantation. CONCLUSION: This study represents another case series describing aniridic fibrosis syndrome and the largest study to report utilization of the type I Boston KPro in such patients. As the fibrosis can cause IOL dislocation, corneal decompensation, hypotony, and retinal detachment, monitoring for aniridic fibrosis syndrome in congenital aniridia with early surgical intervention is recommended. Type I Boston KPro may be considered in the surgical treatment of this condition.

Limbitis secondary to autologous serum eye drops in a patient with atopic keratoconjunctivitis.

Purpose. Report a case of limbitis secondary to autologous serum eye drops in a patient with atopic keratoconjunctivitis. Design. Interventional case report. Methods. A 32-year-old African American female with atopic keratoconjunctivitis (AKC) presented with chronic dry eye and diffuse punctate epithelial erosions refractory to conservative treatment. She was initially managed with cyclosporine ophthalmic 0.05% in addition to preservative-free artificial tears and olopatadine hydrochloride 0.2% for 6 months. She was later placed on autologous serum eye drops (ASEDs) and 4 weeks into treatment developed unilateral limbitis. The limbitis resolved shortly after stopping ASEDs in that eye; however, the drops were continued in the contralateral eye, which subsequently developed limbitis within 2 weeks. ASEDs were discontinued in both eyes, and the patient has remained quiet ever since. Results. Patient with a history of AKC and no prior history of limbitis developed limbitis shortly after starting ASEDs, which resolved promptly after discontinuation of therapy with no subsequent recurrence of inflammation. Conclusion. ASEDs are widely used in the treatment of complicated or treatment refractory dry eye. The potential side effects should be kept in mind when prescribing ASEDs for any patient, especially in those with underlying immunological diseases and circulating inflammatory factors.

Update on limbal stem cell transplantation.

Limbal epithelial stem cells are the primary source of corneal epithelial cell regeneration. Limbal stem cell deficiency (LSCD) can develop in traumatic, immunologic, or genetic diseases that affect the ocular surface. LSCD leads to conjunctivalization, with corneal vascularization and opacification and subsequent loss of vision. Limbal stem cell transplantation is a surgical treatment to address LSCD and restore a corneal epithelial phenotype. Based on the source of cells, limbal transplant can be autologous or allogenic. Many surgical techniques are defined according to the source of the stem cells and the carrier tissues that are used. More recently, ex vivo expanded bioengineered epithelial cells have been used to reconstruct the corneal surface using autologous cells to eliminate the risk of rejection. Before transplantation, a systematic exam of the lids, eyelashes, fornices, and aqueous tears is mandatory and every effort should be made to optimize ocular surface health and control inflammation to enhance the chances of graft survival. Postoperative care is also another major determinant of success. Any factor that destabilizes the ocular surface needs to be addressed. In addition, systemic and topical immunosuppressants are also needed in all allograft recipients. In addition to pre-operative and postoperative care and the surgery itself, the etiology of LSCD also has an impact on the outcome. The prognosis of inflammatory diseases such as Stevens-Johnson syndrome is the worst among disorders causing LSCD.

Midterm outcomes of autologous cultivated limbal stem cell transplantation with or without penetrating keratoplasty.

PURPOSE: To report the midterm outcomes of autologous limbal stem cell transplantation cultivated on amniotic membrane (AM) with or without subsequent penetrating keratoplasty (PKP) in patients with total unilateral limbal stem cell deficiency (LSCD). METHODS: Eight eyes of 8 consecutive patients with unilateral total LSCD underwent autologous limbal stem cell transplantation cultivated on AM. Four eyes underwent subsequent optical PKP. Main outcome measures were corneal vascularization and transparency. RESULTS: The patients were followed for 34.0 +/- 13.5 months (6-48 months). Seven cases had a stable corneal epithelium with marked decrease in opacification and vascularization. Progressive sectorial conjunctivalization was evident in all cases with subsequent PKP at the last follow-up. Primary failure was observed in one case because of exposure. CONCLUSIONS: Transplantation of autologous stem cells cultivated on AM with or without subsequent PKP seems to be an effective way for visual rehabilitation in total LSCD. More work with more cases and longer follow-up are needed to optimize this procedure to provide and maintain an adequate supply of limbal stem cells in these patients.

Correlation between Retinal Nerve Fiber Layer Thickness by Optical Coherence Tomography and Perimetric Parameters in Optic Atrophy.

PURPOSE: To investigate the correlation between retinal nerve fiber layer (RNFL) thickness determined by optical coherence tomography (OCT) and visual field (VF) parameters in patients with optic atrophy. METHODS: This study was performed on 35 eyes of 28 patients with optic atrophy. RNFL thickness was measured by OCT (Carl Zeiss, Jena, Germany) and automated perimetry was performed using the Humphrey Field Analyzer (Carl Zeiss, Jena, Germany). The correlation between RNFL thickness and VF parameters was evaluated. RESULTS: Mean global RNFL thickness was 44.9±27.5 µm which was significantly correlated with mean deviation score on automated perimetry (r=0.493, P=0.003); however, no significant correlation was observed between visual field pattern standard deviation and the corresponding quadrantic RNFL thickness. In a similar manner, no significant association was found between visual acuity and RNLF thickness. CONCLUSION: Mean global RNFL thickness as determined by OCT seems to be correlated with VF defect depth as represented by the mean deviation score on Humphrey VF testing. OCT may be used as an objective diagnostic tool in the evaluation of patients with optic atrophy.

EMLA cream application without occlusive dressing before upper facial botulinum toxin injection: a randomized, double-blind, placebo-controlled trial.

A randomized, double-blind, placebo-controlled clinical trial was conducted among 44 subjects to assess the efficacy of EMLA cream application without occlusive dressing on pain on needling (PN) and pain on injection (PI) felt during multiple botulinum toxin type A (BTA) injections for correction of hyperkinetic upper facial lines. Mean PN score was less than PI score with high correlation and no significant difference. Although both PN and PI scores (visual analog) were less in the EMLA than placebo group, the difference was only statistically significant for PN score. Time intervals between the cream application and BTA injections beyond 60 minutes did not show lower pain score in either type of the pain.