Faculty Bibliography

PURPOSE/OBJECTIVE:To study corneal reinnervation and sensation recovery in Herpes zoster ophthalmicus (HZO). METHODS:Two patients with HZO were studied over time with serial corneal esthesiometry and laser in vivo confocal microscopy (IVCM). A Boston keratoprosthesis type 1 was implanted, and the explanted corneal tissues were examined by immunofluorescence histochemistry for βIII-tubulin to stain for corneal nerves. RESULTS:The initial central corneal IVCM performed in each patient showed a complete lack of the subbasal nerve plexus, which was in accordance with severe loss of sensation (0 of 6 cm) measured by esthesiometry. When IVCM was repeated 2 years later before undergoing surgery, case 1 showed a persistent lack of central subbasal nerves and sensation (0 of 6). In contrast, case 2 showed regeneration of the central subbasal nerves (4786 μm/mm) with partial recovery of corneal sensation (2.5 of 6 cm). Immunostaining of the explanted corneal button in case 1 showed no corneal nerves, whereas case 2 showed central and peripheral corneal nerves. Eight months after surgery, IVCM was again repeated in the donor tissue around the Boston keratoprosthesis in both patients to study innervation of the corneal transplant. Case 1 showed no nerves, whereas case 2 showed new nerves growing from the periphery into the corneal graft. CONCLUSIONS:We demonstrate that regaining corneal innervation and corneal function are possible in patients with HZO as shown by corneal sensation, IVCM, and ex vivo immunostaining, indicating zoster neural damage is not always permanent and it may recover over an extended period of time.

PURPOSE/OBJECTIVE:Idiopathic vitritis is a poorly understood complication after Boston keratoprosthesis surgery with unclear etiology. We sought to determine whether an association exists between periprosthetic corneal tissue loss and the development of idiopathic vitritis in keratoprosthesis recipients. METHODS:Thirteen Boston type I keratoprosthesis recipient eyes with a history of idiopathic vitritis and 34 type I keratoprosthesis recipient eyes with no history of idiopathic vitritis underwent anterior segment optical coherence tomography (AS-OCT) at a median time postoperatively of 2.4 years versus 1.9 years (range, 0.5-14.2 vs. 0.1-13.6 years), respectively. Areas of corneal graft tissue loss ("gaps") around the keratoprosthesis stem were identified and analyzed by 2 masked observers. The difference in the presence, number, and size of gaps was compared between cases and controls. RESULTS:A periprosthetic gap was identified more commonly in idiopathic vitritis cases than in controls on AS-OCT (11/13, 86% vs. 11/34, 33.3%, P < 0.001). The number of gaps between cases and controls was also significantly different (2.6 ± 1.6 vs. 0.5 ± 0.8, P < 0.001), but not the estimated gap area (0.056 ± 0.049 mm² vs. 0.039 ± 0.025 mm², P = 0.22). CONCLUSIONS:A significantly higher proportion of keratoprosthesis recipient eyes with idiopathic vitritis had corneal tissue loss around the keratoprosthesis stem than did controls. Tissue loss could serve as an entry point for debris or bacterial components, triggering idiopathic vitritis. Our study underscores the utility of AS-OCT imaging in the postoperative management of keratoprosthesis patients.

PURPOSE/OBJECTIVE:To describe the clinical and histopathologic features distinguishing an extensive complex choristoma of the epibulbar surface and to address the management of such lesions. METHODS:Clinical history, diagnostic imaging studies, and histopathologic sections stained with hematoxylin and eosin were reviewed from a 2-year-old girl with a congenital conjunctival lesion of the right eye that was surgically excised. RESULTS:The patient clinically displayed an extensive, vascularized amelanotic conjunctival lesion located superotemporally with extension onto the cornea. Her visual acuity was reduced to 20/670. The clinical diagnosis was a large lacrimal gland choristoma with corneal involvement and resulting deprivation amblyopia. The patient underwent an excision of the lesion including the corneal portion, and the ocular surface was reconstructed with amniotic membrane. Histopathologic evaluation disclosed lobules of lacrimal tissue and cartilage plaques, smooth muscle, and nerves consistent with a complex choristoma. Six weeks postoperatively, the visual acuity had improved to 20/180. The patient returned to her local ophthalmologist for amblyopia management. CONCLUSIONS:We emphasize the importance of recognizing lesion-induced amblyopia and the timely performance of appropriate surgery for complex epibulbar choristomas. A differential diagnosis of other congenital epibulbar lesions is provided.

PURPOSE/OBJECTIVE:The aim of this study was to report outcomes of type I Boston keratoprosthesis (KPro) as primary corneal surgery in nonautoimmune corneal disorders. METHODS:In this retrospective, observational, large single-center case series of 43 eyes (37 patients) that were followed for an average of 39 months (1-6 years), primary implantation of the type I Boston KPro was performed in all patients. Visual acuity at year 1, visual acuity at last follow-up, and postoperative complication rates were examined for all eyes. RESULTS:Preoperative best-corrected visual acuity ranged from 20/60 to light perception, with vision of 20/200 or worse in 88%. Vision was ≥20/200 at 1 year in 77% of eyes (P < 0.0001). Complications included retroprosthetic membrane formation (51%), glaucoma progression (47%), corneal melt (19%), and sterile vitritis (14%). CONCLUSIONS:In a large series with long follow-up, primary Boston KPro effectively restored vision. Close follow-up is needed to manage the known complications after Boston KPro.

PURPOSE/OBJECTIVE:The aim of this study was to revisit the clinical paradigm attributed to Boston keratoprosthesis recipients presenting with idiopathic vitreous inflammation. METHODS:A retrospective chart review was performed of keratoprosthesis recipients at Massachusetts Eye and Ear Infirmary, from January 2000 to August 2013, for demographic data, indication(s) for surgery, timing and presentation of vitreous inflammation, and best-corrected visual acuity at baseline, on presentation, and after resolution of vitritis. RESULTS:Twenty-three (23 eyes) of 346 patients developed idiopathic vitreous inflammation after keratoprosthesis implantation. Six of 23 patients presented with signs and symptoms similar to infectious endophthalmitis but were culture negative. The proportion of patients who fit the previous paradigm of sudden painless loss of vision without external signs of infection ("sterile vitritis") at their first presentation with vitritis was only 4 of 23. Vision decline was variable (median, 9 lines on Snellen chart; range, 0-24), as was time to recovery of best vision (median, 8.9 weeks; range, 0.9-36.7). Nine eyes had repeat bouts (43 episodes in 23 patients). Ten of 43 episodes did not recover to baseline vision. Seventeen of 23 eyes with idiopathic vitritis after keratoprosthesis later developed other complications. CONCLUSIONS:The current paradigm for idiopathic vitritis after keratoprosthesis implantation includes sudden painless loss of vision with full recovery of vision on treatment with periocular corticosteroids. However, idiopathic vitritis after keratoprosthesis can also mimic infectious endophthalmitis with pain and external signs of inflammation. Visual loss can be gradual. Vision may not recover to baseline despite treatment. Vitritis may be a part of a common pathway of chronic inflammation after keratoprosthesis.

PURPOSE/OBJECTIVE:To compare the anatomy of the graft-host junction and anterior chamber angle after Boston Keratoprosthesis (KPro) placement using oversized (9.5-mm) and standard (8.5-mm) back plates. METHODS:Six patients with 9.5-mm titanium back plates and 10 patients with 8.5-mm titanium back plates were imaged by anterior segment optical coherence tomography 6 to 12 months after KPro placement. The location of the graft-host junction in relation to the back plate, the corneal thickness at the graft-host junction, and the anterior chamber angle were assessed. The clinical outcomes and incidence of retroprosthetic membrane (RPM) formation in this cohort were retrospectively evaluated. RESULTS:The oversized back plates completely covered the graft-host junction in all quadrants, allowing the complete apposition of the posterior surface of the carrier graft with the host cornea, with decreased graft-host junction wound thickness. The standard back plates covered the posterior aspect of the carrier graft but not the graft-host junction or the host cornea, resulting in a significantly thicker graft-host junction. None of the patients with larger back plates developed a significant RPM during a 12-month follow-up period. One patient with a larger back plate developed a corneal melt at the KPro stem as a result of chronic exposure. CONCLUSIONS:Oversized KPro back plates effectively cover the graft-host junction without any adverse effects on angle anatomy or wound healing. This may be a strategy to provide better wound apposition, reduce RPM formation, and reduce angle closure from iris synechiae to the wound.

PURPOSE/OBJECTIVE:To evaluate clinicopathologically and immunohistochemically a spectrum of conjunctival squamous proliferations. DESIGN/METHODS:Retrospective clinicopathologic study. METHODS:One large cell acanthoma, 7 epidermoid dysplasias, and 4 squamous papillomas were evaluated with microscopy and biomarkers Ki-67, p53, epithelial membrane antigen (EMA), Ber-EP4, AE1, AE3, and 8 individual cytokeratins. Normal associated conjunctiva served as a baseline for interpretation. RESULTS:The large cell acanthoma recurred 4 times but retained its benign histopathologic features. The cells were 2-3 times larger than the keratinocytes of the normal conjunctiva and did not display atypia. Immunohistochemistry revealed a low Ki-67 proliferation index (PI) in the large cell acanthoma compared with high indices in dysplasias and papillomas. p53 was negative in the nuclei of normal epithelium while positive in all neoplasms, most intensely in the dysplasias. Immunostaining showed similar staining patterns for cytokeratins in large cell acanthoma and normal conjunctiva, except for full-thickness CK14 positivity and CK7 negativity in the lesion. Dysplasias generally lost normal CK7 expression and frequently abnormally expressed CK17. The papillomas displayed a normal cytokeratin pattern but exhibited a higher than normal PI and weak p53 positivity. CONCLUSIONS:Conjunctival large cell acanthoma is a morphologically distinctive clonal entity with clinical and immunohistochemical phenotypic characteristics denoting a dysplasia of minimal severity. Because of recurrences without invasion, it requires treatment. Dysplasias exhibited more deviant biomarker abnormalities including frequent aberrant full-thickness CK17 positivity and CK7 negativity. The absence of major cytokeratin derangements in the squamous papillomas may be of ancillary diagnostic value for lesions displaying borderline cytologic features.

Aniridia classically presents with a bilateral congenital absence or malformation of the irides, foveal hypoplasia, and nystagmus, and patients tend to develop visually significant pre-senile cataracts and keratopathy. Additionally, they are at high risk for developing glaucoma. Classic aniridia can be genetically defined as the presence of a PAX6 gene deletion or loss-of-function mutation that results in haploinsufficiency. Variants of aniridia, which include a condition previously referred to as autosomal dominant keratitis, are likely due to PAX6 mutations that lead to partial loss of PAX6 function. Aniridia-associated keratopathy (AAK) is a progressive and potentially debilitating problem affecting aniridic patients. The current treatments for AAK are to replace the limbal stem cells through keratolimbal allograft (KLAL) with or without subsequent keratoplasty for visual rehabilitation, or to implant a Boston type 1 keratoprosthesis. Future therapies for AAK may be aimed at the genetic modification of corneal limbal stem cells.