Endothelial keratoplasty in the management of irido-corneal endothelial syndrome.

PURPOSE: To describe the results of endothelial keratoplasty (EK) in the management of irido-corneal endothelial (ICE) syndrome. DESIGN: Retrospective, consecutive, interventional case series. METHODS: Eight eyes of seven patients underwent EK for corneal edema owing to ICE syndrome. Simultaneous cataract surgery was performed in five eyes. The charts were reviewed for demographics, clinical findings, and outcomes after EK. RESULTS: Mean age was 50.4 years (range 35-59 years). Mean follow-up was 12.5 months (range 6-24 months). Corneal clarity was restored in all eyes and was maintained till the last follow-up. Four patients had acute rise in the intraocular pressure in the post-operative period, which was well controlled on medical treatment. One patient who was non-compliant with medications and regular follow-up advice had progression of glaucomatous disc changes and visual field loss. The best-corrected visual acuity ranged from 20/50-20/30. CONCLUSIONS: EK is a viable option in ICE syndrome. Adequate control of glaucoma is the paramount factor in maintaining good visual acuity in these eyes.

Ocular surface changes in limbal stem cell deficiency caused by chemical injury: a histologic study of excised pannus from recipients of cultured corneal epithelium.

PURPOSE: To report histopathologic changes of the ocular surface pannus in patients with severe limbal stem cell deficiency (LSCD). METHODS: Corneal and conjunctival pannus tissues from 29 patients undergoing ocular reconstruction with cultured limbal cell transplantation were included. The medical records of these patients were reviewed for demographics, aetiologic diagnosis, type of injury, interval between the initial insult and excision of pannus, and medical history involving human amniotic membrane (HAM) or limbal transplantation. The paraffin-embedded tissues were reviewed for epithelial changes, type-degree of fibrosis, degenerative changes, vascular changes, conjunctivalization of corneal surface, and evidence of residual HAM. We attempted a clinicopathologic correlation to understand the pathogenesis of pannus formation in LSCD. RESULTS: The 29 tissues were from 29 eyes of patients with primary aetiology of chemical burn in 89.6% (undetermined in 10.4%) of cases. The pannus showed epithelial hyperplasia in 62%, active fibrosis in 66%, severe inflammation in 21%, giant cell reaction in 28%, and stromal calcification in 14% cases. Goblet cells were seen over the cornea in 64% cases; their absence was associated with squamous metaplasia of the conjunctiva and with long duration of insult. Evidence of residual HAM was noted in 42% cases. CONCLUSIONS: The commonest cause of severe LSCD is alkali-induced injury. Goblet cells over the cornea were seen in 60% of cases. HAM used for ocular surface reconstruction could persist for long periods within the corneal pannus, thus raising the need for further studies with long-term follow-up.

Structural and functional outcome of scleral patch graft.

PURPOSE: To evaluate the visual and structural outcomes of scleral patch grafting in cases of scleral defect. METHODS: The study was a retrospective interventional case series. Medical records of all patients who underwent scleral patch grafting at a tertiary care centre between 1997 and 2003 for scleral defects were reviewed. After removal of all the devitalized tissue, alcohol-preserved full-thickness sclera was tailored to fit the defect and sutured in place. The graft was covered with a conjunctival flap or amniotic membrane. Structural integrity and visual outcome were assessed as the main outcome measures. RESULTS: A total of 13 eyes of 13 patients required scleral patch grafting for scleral defects of varying aetiologies, the most common being necrotizing scleritis following pterygium surgery (40%). The patients were followed up for 6-60 months, an average period of 24.3 months. Tectonic success was achieved in 10 eyes (76.9%). Three complications were noted: endophthalmitis, graft necrosis, and graft dehiscence with uveal prolapse. However, no regrafts were needed. Epithelialization and vascularization were seen in the remaining eyes after an average duration of 3-4 weeks. Visual acuity remained stable in the majority (9/13, 60%), improved in one and deteriorated in three eyes. CONCLUSIONS: Scleral grafting with overlying conjunctival or amniotic membrane graft is an effective and simple measure for preserving globe integrity both structurally and functionally.

Technique of cultivating limbal derived corneal epithelium on human amniotic membrane for clinical transplantation.

BACKGROUND: The technique of transplantation of cultivated limbal epithelium rather than direct limbal tissue isa novel method of "cell therapy" involved in reconstructing the ocular surface in severe limbal stem cell deficiency [LSCD], caused by chemical burns. AIM: To describe a simple feeder-cell free technique of cultivating limbal epithelium on human amniotic membrane[HAM]. MATERIALS AND METHODS: The limbal tissues (2 mm) were harvested from patients with LSCD. These tissues were proliferated in vitro on HAM supplemented by human corneal epithelial cell medium and autologous serum. Cultures covering more > or = 50% area of 2.5 x 5 cm HAM were considered adequate for clinical use. The cultured epithelium was characterized by histopathology and immunophenotyping. RESULTS: A total of 542 cultures out of 250 limbal tissues were cultivated in the laboratory from January 2001 through July 2005. The culture explants showed that clusters of cells emerging from the edge of the explants in one-three days formed a complete monolayer within 10-14 days. In 86% of cultures (464 of 542), the growth was observed within one-two days. Successful explant cultures were observed in 98.5% (534 of 542 cultures) with 91% explant cultures showing an area of > or = 6.25 cm2 (6.25 - 12.5 cm2 range). The cultivated epithelium was terminated between 10-14 days for clinical transplantation. The problems encountered were inadequate growth (2 of 542) and contamination (2 of 542). CONCLUSIONS: We demonstrate a simple technique of generating a sheet of corneal epithelium from a limbal biopsy. This new technique could pave the way for a novel form of cell therapy.

Spontaneous onset corneoscleral hematic cyst.

Corneoscleral cysts are a rare entity. We report a case of spontaneous corneoscleral hematic cyst, which was treated by cyst excision and lamellar corneal patch graft. No recurrence of cyst was noticed during the 6 years of followup.

Outcome of pterygium surgery: analysis over 14 years.

AIM: To report the outcome of pterygium surgery performed at a tertiary eye care centre in South India. METHODS: Retrospective analysis of medical records of 920 patients (989 eyes) with primary and recurrent pterygia operated between January 1988 and December 2001. The demographic variables, surgical technique (bare sclera, primary closure, amniotic membrane transplantation (AMT), conjunctival autograft (CAG), conjunctival-limbal autograft (CLAG), or surgical adjuvants), recurrences and postoperative complications were analysed. RESULTS: A total of 496 (53.9%) were male and 69 (7.5%) had bilateral pterygia. Bare sclera technique was performed in 267 (27.0%) eyes, primary conjunctival closure in 32 (3.2%), AMG in 123 (12.4%), CAG in 429 (43.4%), and CLAG in 70 (7.1%). Adjuvant mitomycin C was used in 44 (4.4%) cases. The mean duration of follow-up was 8.9+/-17.0 and 5.9+/-8.8 months for unilateral primary and recurrent pterygia, respectively. The overall recurrence rate was 178 (18.0%). Following primary and recurrent unilateral pterygium excision respectively, recurrences were noted in 46 (19.4%) and 1 (33.3%) eyes after bare sclera technique, five (16.7%) and 0 after primary closure, 28 (26.7%) and 0 with AMG, 42 (12.2%) and five (31.3%) with CAG, and nine (17.3%) and two (40%) with CLAG. Recurrences were significantly more in males with primary (23.3 vs 10.7%, P<0.0001) and recurrent (26.7 vs 0%, P=0.034) pterygia, and in those below 40 years (25.2 vs 14.8%, P=0.003). CONCLUSION: CAG appears to be an effective modality for primary and recurrent pterygia. Males and patients below 40 years face greater risk of recurrence. Bare sclera technique has an unacceptably high recurrence. Prospective studies comparing CAG, CLAG, and AMG for primary and recurrent pterygia are needed.

Amniotic membrane transplantation in the management of shield ulcers of vernal keratoconjunctivitis.

PURPOSE: To report our experience with amniotic membrane transplantation in the management of severe shield ulcers. DESIGN: Retrospective, interventional, noncomparative case series. PARTICIPANTS: Four patients (seven eyes) with grade 2 (ulcer with opaque base) and grade 3 (plaquelike lesions) shield ulcers not responding to steroid therapy with or without surgical debridement. INTERVENTION: Amniotic membrane transplantation with stromal side down was performed after meticulous debridement of the ulcer. MAIN OUTCOME MEASURES: Healing of the ulcer with no epithelial defect. RESULTS: The ulcers healed with disintegration or retraction of the membrane in all patients within 2 weeks. CONCLUSIONS: Amniotic membrane transplantation in combination with debridement is an effective surgical modality in the management of severe shield ulcers. Further studies are warranted to confirm the efficacy of amniotic membrane transplantation in the management of shield ulcer and its correct position in the treatment algorithm.

Limbal stem cells in health and disease.

Stem cells are present in all self-reviewing tissues and have unique properties. The ocular surface is made up of two distinct types of epithelial cells, constituting the conjunctival and the corneal epithelia. These epithelia are stratified, squamous and non-keratinized. Although anatomically continuous with each other at the corneoscleral limbus, the two cell phenotypes represent quite distinct subpopulations. The stem cells for the cornea are located at the limbus. The microenvironment of the limbus is considered to be important in maintaining stemness of the stem cells. They also act as a "barrier" to conjunctival epithelial cells and prevent them from migrating on to the corneal surface. In certain pathologic conditions, however, the limbal stem cells may be destroyed partially or completely resulting in varying degrees of stem cell deficiency with its characteristic clinical features. These include "conjunctivalization" of the cornea with vascularization, appearance of goblet cells, and an irregular and unstable epithelium. The stem cell deficiency can be managed with auto or allotransplantation of these cells. With the latter option, systemic immunosuppression is required. The stem cells can be expanded ex vivo on a processed human amniotic membrane and transplanted back to ocular surface with stem cell deficiency without the need of immunosuppression.

New perspectives in ocular surface disorders. An integrated approach for diagnosis and management.

The cornea, conjuctiva and the limbus comprise the tissues at the ocular surface. All of them are covered by stratified, squamous, non-keratinizing epithelium and a stable tear film. The ocular surface health is ensured by intimate relationship between ocular surface epithelia and the preocular team film. There are two types of ocular surface failure. The first one is characterized by squamous metaplasia and loss of goblet cells and mucin expression. This is consistent with unstable tear film which is the hallmark of various dry-eye disorders. The second type of ocular surface failure is characterized by the replacement of the normal corneal epithelium in a process called limbal stem cell deficiency. It is essential to establish accurate diagnosis for appropriate management of complex ocular surface disorders. There has been considerable advancement in the understanding of the pathophysiology of ocular surface disease. Management has improved with introduction of the limbal stem cell concept and use of amniotic membrane transplantation.

Amniotic membrane transplantation in acute chemical and thermal injury.

PURPOSE: To present a case of chemical injury and a case of thermal injury treated by amniotic membrane transplantation in acute phase. METHODS: Case reports. An eye with sodium hydroxide injury, opaque cornea, and limbal ischemia of more than 180 degrees and an eye with hot tea injury, opaque cornea, stromal edema, and scarring were treated by amniotic membrane transplantation within the first few weeks of injury. RESULTS: In the eye with sodium hydroxide injury, 4 months after amniotic membrane transplantation, the ocular surface is stable, superficial corneal scarring with vascularization is present, and visual acuity is 20/25. In the eye with thermal injury, 6 months after amniotic membrane transplantation, the ocular surface is stable, but there is superficial scarring and vascularization, and visual acuity is 20/20. CONCLUSIONS: Amniotic membrane transplantation can be considered in chemical injury with severe limbal ischemia and in severe thermal injury in acute phase. Long-term studies are warranted to evaluate further the efficacy of amniotic membrane transplantation in these clinical situations.

Amniotic membrane transplantation for ocular surface reconstruction in Stevens-Johnson syndrome.

PURPOSE: To evaluate amniotic membrane transplantation (AMT) for ocular surface reconstruction in Stevens-Johnson syndrome (SJS). DESIGN: Prospective interventional case series. PARTICIPANTS: Ten consecutive patients (10 eyes) with SJS that underwent AMT as the first step in staged ocular surface reconstruction were included. METHODS: Amniotic membrane was processed under sterile conditions from a fresh placenta obtained from cesarean section in a seronegative pregnant woman and stored at -700 degrees C. Symblepharon release, excision of epibulbar fibrous tissue, and clearing of the fibrovascular membrane over the cornea was performed in all cases. Amniotic membrane covered the entire bulbar surface up to the fornices in five eyes; cornea and the perilimbal area in two eyes; cornea, the inferior bulbar surface, and the lower fornix in two eyes; and cornea and the superior bulbar surface in one eye. Obliterated fornices were deepened by use of fornix-formation sutures in all eyes. Symblepharon ring was placed postoperatively for 3 weeks to 2 months. Mean postoperative follow-up was 13.5 months (SD, +3.8 months; range, 9-30 months). MAIN OUTCOME MEASURES: Restoration of adequate bulbar surface free of symblepharon and good fornix depth were the main outcome measures. RESULTS: Complete corneal reepithelization occurred in all eyes between 1 and 6 weeks. Adequate bulbar surface and fornix depth were achieved in nine eyes, all of which were free of symblepharon at the final follow-up visit. Cicatricial entropion resolved in four of five lower eyelids and one of two upper eyelids after AMT. One patient had a central corneal melt that required or necessitated a penetrating keratoplasty. CONCLUSIONS: AMT restores adequate bulbar surface and fornix depth and prevents recurrence of symblepharon in severe cases of SJS.

Use of ultrasound biomicroscopic evaluation in preoperative planning of penetrating keratoplasty.

PURPOSE: To evaluate the use of ultrasound biomicroscopy (UBM) in examining the status of anterior-segment structures in eyes with corneal opacification. METHODS: Evaluation with UBM was performed between 1 and 2 weeks before surgery in 21 patients (21 eyes) with corneal opacities who were scheduled for penetrating keratoplasty. UBM findings were correlated with the findings noted during penetrating keratoplasty. The efficacy of UBM evaluation was calculated in terms of positive and negative predictive values (PPVs and NPVs) for the presence or absence of each finding. RESULTS: Seventeen eyes had either aphakic or pseudophakic bullous keratopathy (ABK or PBK). UBM findings of anterior synechiae, peripheral anterior synechiae, posterior synechiae, peripheral and sector iridectomies positively correlated with those observed during surgery in five (55.6%) of nine locations, 19 (73.1%) of 26 locations, 12 (80%) of 15 locations, eight (88.9%) of nine locations) and six (85.7%) of seven locations, respectively. The NPVs for these findings were 100%, six (54.5%) of 11 locations), 10 (71.4%) of 14 locations, 12 (100%) of 12 locations, and 14 (100%) of 14 locations, respectively. Correlation for findings pertaining to the posterior capsule (PC) were presence of PC/PC remnants [PPV, 13 (92.9%) of 14 locations; NPV, two (66.7%) of three locations], presence of central PC tears [PPV, two (66.7%) of three locations], intactness of PC [PPV, six (85.7%) of seven locations], and PC thickening [PPV, 13 (81.25%) of 16 locations; NPV, four (100%) of four locations]. For vitreous in the anterior chamber, the PPV was eight (100%) of eight locations, and NPV was 12 (92.3%) of 13 locations. Pseudophakos-related information in eyes with PBK showed a PPV of 100% for presence, centration, and anatomic location (seven of seven, four of four, and seven of seven locations, respectively). CONCLUSION: In eyes with corneal opacity, UBM determines the status of various anterior-segment structures. It is thus a useful adjunct in the preoperative planning and prognostication of patients requiring penetrating keratoplasty.

Krill protease effects on wound healing after corneal alkali burn.

PURPOSE: To study the effect of a novel protease in the development and progression of corneal ulceration secondary to alkali burning. METHODS: By using a 4N alkali burn model of corneal ulceration in rabbits, the effects and efficacy of topical application of a novel protease (PHM-101) capable of degrading metalloproteinases was studied for 28 days of treatment and 7 days off treatment for its effect on corneal ulceration and recurrent erosion. RESULTS: At day 28, both the protease- and placebo-treated groups had different numbers of eyes showing reepithelialization (nine (45%) of 20 and six (33%) of 18, respectively]. By day 35 the protease-treated group had significantly fewer recurrent epithelial defects [two (13%) of 15 vs. eight (61%) of 13; p = 0.02]. Similarly, at day 35 the protease-treated group showed significantly less corneal ulceration [two (13%) of 15 vs. six (46%) of 13; p = 0.02], and those ulcers were of a lesser severity (three units vs. 17.76 units). No difference was found in the degree of stromal edema or neovascularization, nor was there any difference in histopathologic characteristics of inflammatory cell infiltration and corneal scarring. CONCLUSION: We conclude that this novel protease is efficient in reducing recurrent corneal epithelial defects and stromal ulceration after alkali burning.

Leukocyte adhesion molecule expression in scleritis.

OBJECTIVE: To analyze the expression and cellular distribution of intercellular adhesion molecule 1, E-selectin (endothelial leukocyte adhesion molecule), vascular cell adhesion molecule 1, very late antigen 4, and lymphocyte function associated antigen 1 (LFA-1) in diseased and normal human sclera. METHODS: Monoclonal antibodies to vascular cell adhesion molecule 1, very late antigen 4, intercellular adhesion molecule 1, LFA-1, and E-selectin were used to perform immunohistochemical staining on frozen sections of 16 cryopreserved human sclera specimens and 5 conjunctival specimens. RESULTS: The normal human sclera did not express any of the adhesion molecules. The expression of LFA-1 was dramatic in all the scleral and conjunctival specimens on the inflammatory cells. Intercellular adhesion molecule 1, the ligand for LFA-1, was expressed in 7 of 12 scleral specimens. Furthermore, the expression of LFA-1 and intercellular adhesion molecule 1 were focally present in areas of inflammatory infiltrate. E-selectin expression was detected on the vascular endothelial cells in 8 of 12 patients. There was variable expression of vascular cell adhesion molecule 1 and very late antigen 4 in the inflamed sclera and conjunctiva. CONCLUSIONS: Our results demonstrate the presence of LFA-1 in the sclera and in the conjunctiva of patients with scleritis. Variable expression of other leukocyte adhesion molecules was noted in the sclera and the conjunctiva of these patients.

Costimulatory molecules in ocular cicatricial pemphigoid.

PURPOSE: To examine normal and inflamed conjunctiva from patients with ocular cicatricial pemphigoid (OCP) for the presence of costimulatory molecule CD28 and its ligands B7-1 (CD80) and B7-2 (CD86). METHODS: Conjunctival biopsy specimens from 12 patients with OCP and from five healthy persons undergoing cataract surgery were analyzed by light microscopy and immunohistochemical examination with monoclonal antibody probes for CD28, B7-1, and B7-2 molecules and for mononuclear cell subtypes. RESULTS: Epithelium of OCP conjunctiva showed more Langerhans' cells, B7-1-positive (+) cells, and B7-2 expression (ratio of B7-2-positive cells to antigen-presenting cells). In the substantia propria, OCP specimens showed significantly increased numbers of T cells (CD3 +), macrophages (CD68+), CD28+ cells, B7-2+ cells (CD86+), Langerhans' cells (CD1a), and B7-1+ cells (CD80). Most of the B7-2+ cells, macrophages, and Langerhans' cells were located subepithelially. B7-2 expression was significantly higher in OCP conjunctival substantia propria compared with normal conjunctiva. CONCLUSIONS: The results of this study indicate that the expression of the costimulatory molecule B7-2 is upregulated in conjunctiva of patients with active OCP. This increased subepithelial B7-2 expression may contribute to the sustained immune activation in OCP conjunctiva.

Mooren's ulcer: current concepts in management.

Mooren's ulcer is strictly a peripheral ulcerative keratitis (PUK) with no associated scleritis. It occurs completely in absence of any diagnosable systemic disorder that could be responsible for the progressive destruction of the cornea. The aetiology of Mooren's ulcer remains uncertain. However, recent studies indicate that it is an autoimmune disease directed against a specific target molecule in the corneal stroma, probably triggered in genetically susceptible individuals by one of several possible provocateurs. Advances have been made in the management of this disease. Immunosuppressive therapy has been shown increasingly successful in patients unresponsive to conventional treatment and in bilateral progressive destructive ocular disease.