Faculty Bibliography

PURPOSE:To assess outcomes and glaucoma management in eyes with aniridia following Boston type 1 Keratoprosthesis (KPro) implantation. DESIGN:Retrospective, interventional comparative case series. METHODS:The population included patients with aniridia and patients with other preoperative diagnoses (excluding Stevens-Johnson syndrome, mucous membrane pemphigoid, and congenital disorders) who underwent KPro implantation at Massachusetts Eye and Ear with at least 2 years of follow-up. One eye per patient was selected based on the longer follow-up time. The main outcome was intermediate and long-term outcomes related to glaucoma. RESULTS:The aniridia (n = 22) and comparison (n = 61) groups had similar preoperative visual acuity (VA, mean ± standard deviation, 1.86 ± 0.52 logMAR, P = .33) and follow-up time (65.6 ± 26.3 months, P = .25). Before KPro implantation, eyes with aniridia had more glaucoma (76.2%) and glaucoma surgery (57.1%) than comparison eyes (51.8%, P = .053; 23.2%, P = .005, respectively). More Ahmed valves were co-implanted with KPro in aniridia (47.6%) vs comparison eyes (17.9%, P = .008). At final follow-up, more aniridia eyes had glaucoma (90.5%) than comparison eyes (64.3%, P = .02), but the 2 groups had similar percentages of eyes with cup-to-disc ratio (CDR) >0.8 (23.8% vs. 30.4%, P = .57) or CDR progression of ≥0.2 (42.9% vs 44.6%, P = .89, respectively). None of the eyes with prophylactic tube implantation developed glaucoma. Eyes with and without aniridia did not differ in post-KPro VA improvement (72.7%, 72.1%, P = .96), and final VA (1.28 ± 0.79 logMAR, 1.23 ± 0.98 logMAR, P = .51). CONCLUSION:Despite a higher glaucoma prevalence, eyes with aniridia achieved similar VA as comparison eyes with more than 5 years of mean follow-up time. Boston KPro offers satisfactory visual rehabilitation in aniridia when glaucoma is managed aggressively.

Purpose: Boston keratoprosthesis (KPro) patients are prone to glaucoma even with well-controlled intraocular pressure (IOP). Recent experimental data have shown that soluble tumor necrosis factor alpha (TNF-α) after ocular injury may contribute to progressive retinal damage and subsequent glaucoma. This study evaluates the blood plasma levels of soluble TNF-α, TNF receptors 1 (TNFR1) and 2 (TNFR2), and leptin in patients with Boston type I KPro. Methods: Venous blood samples were collected from KPro patients with glaucoma (KPro G, n = 19), KPro patients without glaucoma (KPro NoG, n = 12), primary angle closure glaucoma without KPro (PACG, n = 13), and narrow angles without glaucoma or KPro (NA, n = 21). TNF-α, TNFR1, TNFR2, and leptin levels were quantified using the enzyme-linked immunosorbent assay. Erythrocyte sedimentation rate (ESR) was assessed using the Westergren test. Patients with underlying autoimmune conditions or diabetes were excluded from the study. Results: All groups had similar age, body mass index (BMI), IOP, and ESR (p ≥ 0.11). The mean time from KPro surgery to blood draw was 5.3 ± 3.7 years. Compared to NA patients (0.72 ± 0.3 pg/ml), KPro G and KPro NoG patients had higher blood plasma levels of TNF-α (1.18 ± 0.58 pg/ml, p = 0.006; 1.16 ± 0.50 pg/ml, p = 0.04, respectively). Similarly, KPro G patients had higher blood plasma levels of TNFR2 (2768 ± 1368 pg/ml) than NA patients (2020 ± 435 pg/ml, p = 0.048). In multivariate analysis, KPro status remained positively associated with TNF-α levels (β = 0.36; 95% confidence intervals [CI]: 0.14-0.58; p = 0.002) and TNFR2 levels (β = 458.3; 95% CI: 32.8-883.7; p = 0.035) after adjusting for age, gender, BMI, glaucoma status, and ESR. TNFR1 and leptin levels were not significantly different in the study groups. Conclusions: We detected elevated serum levels of TNF-α and TNFR2 in KPro patients. Longitudinal studies are needed to establish TNF-α and TNFR2 as serum biomarkers related to KPro surgery. Abbreviations: BCVA: best corrected visual acuity; BMI: body mass index; CDR: cup-to-disc ratio; EDTA: ethylenediaminetetraacetic acid; ELISA: enzyme-linked immunosorbent assay; ESR: erythrocyte sedimentation rate; HVF: Humphrey visual field; IOP: intraocular pressure; KPro G: keratoprosthesis with glaucoma; KPro NoG: keratoprosthesis without glaucoma; KPro: keratoprosthesis; MD: mean deviation; NA: narrow angle; non-KPro: without keratoprosthesis; PACG: primary angle closure glaucoma; RNFL: retinal nerve fiber layer; TNF-α: tumor necrosis factor alpha; TNFR1: tumor necrosis factor receptor 1; TNFR2: tumor necrosis factor receptor 2.

Fuchs endothelial corneal dystrophy (FECD) is the most common indication for corneal transplantation in the United States, accounting 36% of the almost 47,000 transplants performed in 2016. Although the surgical management of FECD has undergone a revolution over the past 20 years, its pathogenesis remains elusive, with multiple putative disease pathways and an ever increasing number of candidate genes thought to play a role. This review will summarize the recent advancements in our understanding of the biology of FECD, including potential parallels with neurodegenerative disease like amyotrophic lateral sclerosis and will highlight prospects for future treatment advances.

PURPOSE/OBJECTIVE:To compare the outcomes of Boston keratoprosthesis type 1 implantation after failed keratoplasty in patients who are blind or sighted in the contralateral eye. METHODS:Retrospective comparative case series of Boston keratoprosthesis type I recipients performed for failed keratoplasty, between January 1, 2008, and June 30, 2016, at a single center. Patients were divided based on the best-corrected visual acuity in the contralateral eye at the time of surgery: group I, ≤20/200, and Group II, >20/200. Preoperative diagnoses, postoperative visual acuity, device retention, and postoperative complications were compared. RESULTS:Group I (37 eyes) and group II (36 eyes) had similar demographics, median preoperative best-corrected visual acuity (count fingers) in the operated eye, and median duration of postoperative follow-up (37.4 vs. 45.2 months, respectively). Keratoprosthesis retention after the first year postimplantation was significantly better in group I versus group II (P = 0.038). Sterile vitritis and sterile keratolysis occurred more frequently in group II compared with group I (P = 0.013 and P = 0.056, respectively). At final examination, visual outcomes were not significantly different between the 2 groups. CONCLUSIONS:Most patients with failed keratoplasty who were implanted with a Boston keratoprosthesis type I experienced improved vision, and visual acuity of the contralateral eye did not seem to influence the visual outcome of surgery. However, patients with good vision in the contralateral eye were more likely to experience complications, possibly because of reduced vigilance when the other eye has ambulatory vision.

OBJECTIVES/OBJECTIVE:To examine clinical outcomes of oversized titanium back plates in type I Boston keratoprosthesis (KPro) implantation. METHODS:Retrospective study of 22 sequential eyes (20 patients) undergoing type I KPro implantation with an oversized titanium back plate (larger than trephined wound diameter by 1.0 mm or more), performed by a single surgeon (K.A.C.) from June 2010 to November 2014. Data were collected regarding preoperative eye characteristics, surgical details, and postoperative clinical outcomes. RESULTS:Mean follow-up time per eye was 24.1±14.9 months. All eyes had improved vision after surgery; 13 eyes (59.1%) maintained visual acuity improvement at last follow-up. Initial KPro's were retained in 19 eyes (86.4%); one eye required KPro replacement. Primary retroprosthetic membrane (RPM) developed in three eyes (13.6%), with similar occurrence in aniridic (14.3%) and nonaniridic eyes (13.3%). Secondary RPM's developed in two eyes (9.1%) after vitritis (one eye) and retinal and choroidal detachment (one eye). Glaucoma was a common comorbidity: 2 of 14 eyes (14.3%) with preoperative glaucoma had glaucoma progression, and 4 of 8 eyes (50.0%) without preoperative glaucoma developed glaucoma postoperatively. Other postoperative complications included retinal detachment (5 eyes, 22.7%) and idiopathic vitritis (3 eyes, 13.6%). CONCLUSIONS:Oversized titanium KPro back plates are associated with a low rate of primary RPM formation and may have particular utility in reducing primary RPM formation in aniridic eyes. Glaucoma remains a challenge in postoperative KPro management. Complex eyes, at increased risk of postoperative complications, require careful management.

OBJECTIVES/OBJECTIVE:To describe the postmortem histologic features after an unsuccessful Descemet membrane endothelial transfer (DMET) and assess any potential clinical implications. METHODS:Postmortem, an eye from a patient who previously underwent unsuccessful DMET for pseudophakic bullous keratopathy (PPBK) was harvested and processed for morphologic evaluation. RESULTS:Clinically and histologically, the host cornea showed evidence of diffuse stromal edema. Although the edges of the surgical descemetorhexis were well visualized, there was no evidence of endothelial migration or repopulation of the posterior stroma from any direction. A multilayered, retrocorneal membrane was present that appeared to originate from the trabecular meshwork. CONCLUSIONS:Descemet membrane endothelial transfer and "descemetorhexis alone" may be insufficient treatment for eyes operated on for PPBK, that is, eyes with a significantly depleted or dysfunctional endothelium.

PURPOSE/OBJECTIVE:To propose a new treatment paradigm for chemical burns to the eye - in the acute and chronic phases. METHODS:Recent laboratory and clinical data on the biology and treatment of chemical burns are analyzed. RESULTS:Corneal blindness from chemical burns can now be successfully treated with a keratoprosthesis, on immediate and intermediate bases. Long term outcomes, however, are hampered by early retinal damage causing glaucoma. New data suggest that rapid diffusion of inflammatory cytokines posteriorly (TNF-α, etc) can severely damage the ganglion cells. Prompt anti-TNF-α treatment is markedly neuroprotective. Long term profound reduction of the intraocular pressure is also vital. CONCLUSION/CONCLUSIONS:A new regimen, in addition to standard treatment, for severe chemical burns is proposed. This involves tumor necrosis factor alpha (TNF-α) inhibition promptly after the accident (primarily for retinal neuroprotection), prophylactic maximal lowering of the intraocular pressure (starting immediately), and keratoprosthesis implantation in a later quiet state.