Short-Term Outcomes of Pediatric Keratoprosthesis With the Near-Complete Conjunctival Flap.

PURPOSE: The Boston keratoprosthesis (KPro) has been used for certain indications in pediatric patients with congenital corneal opacities. Here, we describe the use of a near-complete conjunctival flap at the time of Boston type 1 KPro surgery in pediatric patients, with the goal of improving pediatric KPro outcomes. METHODS: We performed a retrospective chart review of 21 eyes from 16 patients who received their first KPro before the age of 18 years at a tertiary care center in Rochester, NY. Surgeries were performed between 2011 and 2017 (3 years before and after the incorporation of a conjunctival flap, which began in 2014 as part of the pediatric KPro procedure). Patients who had a minimum 1-year postoperative follow-up, or had corneal melts within 1 year of KPro implantation, were included in our study. The main outcome measure in this study was a comparison of the number of complications that required surgical intervention, including retroprosthetic membrane, corneal melt, retinal detachment, and endophthalmitis, in eyes that received KPro implantation without a conjunctival flap compared with eyes that received KPro implantation with a conjunctival flap. Change in the visual acuity up to 1 year postoperatively was also measured. RESULTS: Ten eyes received KPro with no conjunctival flap, and 11 eyes received KPro with a near-complete conjunctival flap. After 1-year postoperative follow-up, eyes receiving a KPro with a conjunctival flap had fewer KPro-related complications requiring surgical intervention (5 vs. 16, P = 0.0002). Corneal melt was seen in 2 of 11 (18%) eyes in the conjunctival flap group and 5 of 10 (50%) eyes in the nonflap group (P = 0.12). No eyes developed endophthalmitis in the flap group, whereas 1 of 10 (10%) eyes developed endophthalmitis in the nonflap group. Visual acuity at 1-year follow-up improved in 9 of 11 (82%) eyes in the flap group compared with 5 of 10 (50%) eyes in the nonflap group (P = 0.3). CONCLUSIONS: Implementation of a conjunctival flap in pediatric KPro may help decrease the short-term postoperative complications requiring surgical procedures and may lead to improved visual acuity after 1 year. Further investigation, including longer-term follow-up, is needed to better understand how the described technique affects surgical outcomes in children.

ISOPT Clinical Hot Topic Panel Discussion on Cornea Anterior Segment Disease.

The cornea and its adnexa pose a unique situation of a tightly defined set of requirements for its function. This includes: transparency, perfect built to obtain appropriate refractive power, protective barrier from microbial invaders. Moreso, the cornea also endures extreme external physical conditions (temperature, high and low humidity, winds and alike). All these functions are maintained while preserving a constant state of homogenous wetting. Toward that end the cornea is equipped with an elaborated network of sensory neural network. While enabling the blinking reflex and maintaining the physiological steady state of wetting, this neural network also makes the cornea prone to the discomfort that with or without associated changes seen on medical examination. ISOPT Clinical 2018 discussion touched upon this hypercomplex situation, addressing the role of inflammation and its resulting discomfort in dry eye conditions. The discussion also engulfed the emerging neuropathic pain syndrome that is recently gaining more attention. Another related topic was the utilization of autologous serum tears and its ability to provide amelioration to desperate patients. Finally, the panel discussed the issue of treating corneal infection, including when and how to utilize steroids in the course of therapy. We assume the reader will find interest in this discussion that directly addresses issues seen day in and day out in our busy clinics.

Chemical Burns of the Eye: The Role of Retinal Injury and New Therapeutic Possibilities.

PURPOSE: 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: 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.

Keratoprosthesis in Ectodermal Dysplasia.

PURPOSE: To describe the complex surgical management and novel medical approach for a keratoprosthesis (KPro Boston type I) in a monocular, 73-year-old patient with ectodermal dysplasia and chronic, noninfectious corneal necrosis. METHODS: Best-corrected visual acuity (BCVA) was measured with Snellen letters. Surgical intervention included an amniotic membrane graft, complete replacement of the KPro, conjunctival flap graft, corneal donor tissue grafts combined with inferior rectus muscle advancement, periosteal tissue graft, tarso-conjunctival flap construction, and symblepharolysis. Infliximab was used as a medical adjunctive therapy. RESULTS: Initial KPro placement provided a BCVA of 20/25 and long-term stability. Subsequent chronic melting at the optic border necessitated numerous surgeries to prevent extrusion and failure. Ultimate fistulization was addressed with the formation of a surgical pocket. The addition of infliximab promoted ocular surface stability, and the patient has maintained a BCVA of 20/80. CONCLUSIONS: Ectodermal dysplasia can result in eyelid and corneal abnormalities, requiring a KPro for visual restoration. In the setting of chronic, sterile corneal melt, novel surgical approaches and the off-label use of infliximab allowed for visual rehabilitation.

Protective effect of soft contact lenses after Boston keratoprosthesis.

PURPOSE: To evaluate associations between preoperative diagnosis, soft contact lens (SCL) retention and complications. METHODS: A retrospective chart review was conducted of 92 adult patients (103 eyes) who received a Boston keratoprosthesis type I at the Massachusetts's Eye and Ear Infirmary or the Flaum Eye Institute. Records were reviewed for preoperative diagnosis, SCL retention and subsequent complications. Preoperative categories included 16 autoimmune (Stevens-Johnson syndrome, ocular cicatricial pemphigoid, rheumatoid arthritis and uveitis), 9 chemical injury and 67 'other' (aniridia, postoperative infection, dystrophies, keratopathies) patients. RESULTS: 50% of the lenses had been lost the first time after about a year. A subset (n=17) experienced more than 2 SCL losses per year; this group is comprised of 1 patient with autoimmune diseases, 2 patients with chemical injuries and 14 patients with 'other' diseases. The preoperative diagnosis was not predictive of contact lens retention. However, multivariate analysis demonstrated that the absence of a contact lens was an independent risk factor for postoperative complications, such as corneal melts with or without aqueous humour leak/extrusion and infections. CONCLUSIONS: Presence of a contact lens after Boston keratoprosthesis implantation decreases the risk of postoperative complications; this has been clinically experienced by ophthalmologists, but never before has the benefit of contact lens use in this patient population been statistically documented.

Outcomes of Repeat Boston Type 1 Keratoprosthesis Implantation.

PURPOSE: To describe the outcomes and prognostic characteristics of patients who had a repeat Boston type 1 keratoprosthesis (KPro) implantation. DESIGN: Retrospective case series. METHODS: setting: Data regarding preoperative clinical and demographic characteristics and postoperative course during initial and repeat KPro placement were collected at multiple centers across the country. PATIENTS: Forty-eight eyes underwent explantation of KPro owing to complications between September 2003 and August 2014 at 5 participating tertiary eye care centers in the United States. Of those, 36 eyes that received a subsequent replacement device were included. MAIN OUTCOME MEASURES: Visual acuity (VA) outcomes and postoperative complications. RESULTS: Ocular surface disease was significantly more common in eyes that required a device explantation, compared to those that retained the device (P < .001). Sixty-seven percent of eyes (24/36) achieved VA ≥ 20/200 vision after the repeat KPro. The probability of these 24 eyes maintaining VA ≥ 20/200 after the repeat KPro was 87% at 1 year and 75% at 2 years. Predictors of the ability to maintain vision ≥ 20/200 following surgery were a better last-recorded vision before explantation (P = .0002) and better vision immediately after repeat KPro (P < .001). CONCLUSION: Ocular surface disease and its complications were associated with more frequent device removal. In these patients, repeat KPro resulted in restoration of vision. A reasonable visual acuity prior to device removal was associated with favorable long-term postoperative visual acuity and retention.

Temperatures of the Ocular Surface, Lid, and Periorbital Regions of Sjögren's, Evaporative, and Aqueous-Deficient Dry Eyes Relative to Normals.

PURPOSE: To compare the temperatures of the ocular surface, eyelid, and periorbital skin in normal eyes with Sjögren's syndrome (SS) eyes, evaporative dry eyes (EDE), and aqueous deficient dry eyes (ADDE). METHODS: 10 eyes were analyzed in each age-matched group (normal, SS, EDE, and ADDE). A noninvasive infrared thermal camera captured two-dimensional images in three regions of interest (ROI) in each of three areas: the ocular surface, the upper eyelid, and the periorbital skin within a controlled environmental chamber. Mean temperatures in each ROI were calculated from the videos. Ocular surface time-segmented cooling rates were calculated over a 5-s blink interval. RESULTS: Relative to normal eyes, dry eyes had lower initial central OSTs (SS -0.71°C, EDE -0.55°C, ADDE -0.95°C, KW P<.0001) and lower central upper lid temperatures (SS -0.24°C, ADDE -0.51°C, and EDE -0.54°C, KW P<.0001). ADDE eyes had the lowest initial central OST (P<.0001), while EDE eyes had the lowest central lid temperature and lower periorbital temperatures (P<.0001). Over the 5-s interblink interval, the greatest rate of temperature loss occurred following eyelid opening, but varied by group (normals -0.52, SS -0.73, EDE -0.63, and ADDE -0.75°C/s). The ADDE group also had the most substantial heat loss over the 5-s interblink interval (-0.97°C). CONCLUSIONS: Differences in OST may be related to thermal differences in lids and periorbita along with an altered tear film. Thermography of the ocular surface, lids, and surrounding tissues may help to differentiate between different etiologies of dry eye.

Thermal analysis of dry eye subjects and the thermal impulse perturbation model of ocular surface.

In this study, we explore the usage of ocular surface temperature (OST) decay patterns to distinguished between dry eye patients with aqueous deficient dry eye (ADDE) and meibomian gland dysfunction (MGD). The OST profiles of 20 dry eye subjects were measured by a long-wave infrared thermal camera in a standardized environment (24 °C, and relative humidity (RH) 40%). The subjects were instructed to blink every 5 s after 20 âˆ¼ 25 min acclimation. Exponential decay curves were fit to the average temperature within a region of the central cornea. We find the MGD subjects have both a higher initial temperature (p < 0.022) and a higher asymptotic temperature (p < 0.007) than the ADDE subjects. We hypothesize the temperature difference among the subpopulations is due to tear volume and heat transfer mechanisms. To study the validity of our claim, we develop a mathematical model, referred to as the thermal impulse perturbation (TIP) model. We conclude that long-wave-infrared thermal imaging is a plausible tool in assisting with the classification of dry eye patient.

Long-term outcomes of boston type 1 keratoprosthesis implantation: a retrospective multicenter cohort.

PURPOSE: To study the long-term outcomes of Boston type 1 keratoprosthesis (KPro) surgery. DESIGN: Retrospective, multicenter case series. PARTICIPANTS: A total of 158 eyes of 150 patients underwent KPro implantation at 5 participating tertiary centers in the United States between January 2003 and December 2006. Of those, 139 eyes of 133 patients were included in the analyses. METHODS: The medical records of consecutive adult patients who received KPro surgery were reviewed. All patients with at least 1 postoperative visit were retained in the outcomes analyses. In eyes in which a repeat KPro procedure was performed, only the outcomes of the initial surgery were analyzed. MAIN OUTCOME MEASURES: Visual acuity (VA) outcomes, postoperative complications, and device retention. RESULTS: The mean follow-up was 46.7 ± 26 months with all but 4 eyes having at least 6 months of follow-up. Preoperatively, only 10.8% of the eyes had VA of ≥ 20/200. Postoperatively, the VA in 70% of eyes improved to ≥ 20/200. The probability of maintaining VA of ≥ 20/200 at 7 years was 50%. The device retention rate was estimated at 67% at 7 years. The 7-year cumulative incidence of complications was 49.7% for retroprosthetic membrane formation, 21.6% for glaucoma surgery, 18.6% for retinal detachment, and 15.5% for endophthalmitis. CONCLUSIONS: Although the risk for complications with longer follow-up seemed to increase, this large multicenter cohort demonstrates favorable outcomes with KPro, with a large number of patients achieving and retaining useful vision over a 7-year period.

Measurement of a multi-layered tear film phantom using optical coherence tomography and statistical decision theory.

To extend our understanding of tear film dynamics for the management of dry eye disease, we propose a method to optically sense the tear film and estimate simultaneously the thicknesses of the lipid and aqueous layers. The proposed method, SDT-OCT, combines ultra-high axial resolution optical coherence tomography (OCT) and a robust estimator based on statistical decision theory (SDT) to achieve thickness measurements at the nanometer scale. Unlike conventional Fourier-domain OCT where peak detection of layers occurs in Fourier space, in SDT-OCT thickness is estimated using statistical decision theory directly on the raw spectra acquired with the OCT system. In this paper, we demonstrate in simulation that a customized OCT system tailored to ~1 µm axial point spread function (FWHM) in the corneal tissue, combined with the maximum-likelihood estimator, can estimate thicknesses of the nanometer-scale lipid and micron-scale aqueous layers of the tear film, simultaneously, with nanometer precision. This capability was validated in experiments using a physical phantom that consists of two layers of optical coatings that mimic the lipid and aqueous layers of the tear film.

Maximum-likelihood estimation in Optical Coherence Tomography in the context of the tear film dynamics.

Understanding tear film dynamics is a prerequisite for advancing the management of Dry Eye Disease (DED). In this paper, we discuss the use of optical coherence tomography (OCT) and statistical decision theory to analyze the tear film dynamics of a digital phantom. We implement a maximum-likelihood (ML) estimator to interpret OCT data based on mathematical models of Fourier-Domain OCT and the tear film. With the methodology of task-based assessment, we quantify the tradeoffs among key imaging system parameters. We find, on the assumption that the broadband light source is characterized by circular Gaussian statistics, ML estimates of 40 nm +/- 4 nm for an axial resolution of 1 µm and an integration time of 5 µs. Finally, the estimator is validated with a digital phantom of tear film dynamics, which reveals estimates of nanometer precision.

Phantom study of tear film dynamics with optical coherence tomography and maximum-likelihood estimation.

In this Letter, we implement a maximum-likelihood estimator to interpret optical coherence tomography (OCT) data for the first time, based on Fourier-domain OCT and a two-interface tear film model. We use the root mean square error as a figure of merit to quantify the system performance of estimating the tear film thickness. With the methodology of task-based assessment, we study the trade-off between system imaging speed (temporal resolution of the dynamics) and the precision of the estimation. Finally, the estimator is validated with a digital tear-film dynamics phantom.

The use of precut, γ-irradiated corneal lenticules in Boston type 1 keratoprosthesis implantation.

PURPOSE: To report the use of a sterile, γ-irradiated corneal tissue without viable endothelium (VisionGraft Sterile Cornea; Tissue Banks International) in lieu of fresh donor cornea in Boston type 1 keratoprosthesis (KPro) implantation. DESIGN: Retrospective, interventional small case series. METHODS: Eleven eyes of 11 patients underwent Boston type 1 keratoprosthesis implantation using VisionGraft Sterile Cornea between April 2009 and October 2010. Precut donut-shaped corneal lenticules, using femtosecond laser, measuring 8.5 mm in diameter with a 3-mm central hole were used. RESULTS: Surgical procedures were uneventful. Complete corneal re-epithelization was noted within 10 days in all cases. No complications related to the donor cornea (eg, stromal necrosis, wound leak, or device extrusion) occurred over an average follow-up of 16.5 months. CONCLUSIONS: VisionGraft Sterile Cornea eliminates the need for use of fresh donor corneal tissue for Boston type 1 keratoprosthesis procedures, which makes this procedure a viable sight-restoring option when donor corneal tissues are not readily available.

Novel formulation of glycerin 1% artificial tears extends tear film break-up time compared with Systane lubricant eye drops.

PURPOSE: To evaluate the effectiveness of glycerin 1% formulated with the novel and proprietary ophthalmic excipient poly(l-lysine)-graft-poly(ethylene glycol) (PLL-g-PEG) (Eyeon Particle Sciences LLC) in extending tear film break-up time (TFBUT) compared with a market-leading artificial tear formulation of propylene glycol (0.3%) and polyethylene glycol (0.4%) (Systane(®) Lubricant Eye Drops; Alcon, Fort Worth, TX). METHODS: This prospective single-center, single visit, randomized, double-masked exploratory trial compared the new formulation and Systane using TFBUT. Noninvasive break-up time (NIBUT) was measured in subjects with asymptomatic to mild (n=5), mild to moderate (n=5), and moderate to severe (n=6) dry eye disease using the TearscopePlus™ at pre-instillation and again at 15, 30, 60, and 120 min after instillation. Fluorescein break-up time (FBUT) was measured at 120 min after instillation. RESULTS: At 15 min (N=16), the new formulation extended mean NIBUT by 14.67 s (P=0.05) compared with 7.40 s (P=0.34) by Systane. The new formulation had a mean FBUT of 4.92 s longer than Systane at 120 min (P=0.12). With outliers removed (N=13), the difference between the mean NIBUT change from baseline for the new formulation and Systane at 120 min was statistically significant (P=0.03). CONCLUSIONS: This study demonstrates that PLL-g-PEG as a polymer excipient in artificial tears is effective in improving the performance of demulcents to significantly prolong NIBUT at 15 min, and that protective activity from this artificial tear product for 2 or more hours after eye drop instillation is possible.

Integrated multimodal metrology for objective and noninvasive tear evaluation.

The clinical tests used to assess tear film and diagnose dry eye are invasive and produce results that are different from natural tear characteristics. There is a need to objectively and noninvasively assess tear parameters under controlled environmental circumstances to refine dry eye diagnosis and therapy. We have developed multimodal tear imaging systems integrated in a chamber in which individual environmental factors can be precisely varied to investigate their impacts on tear parameters. With the custom-built high-resolution wavefront sensor combined with placido disc, it is possible to objectively detect two-dimensional tear breakups in real time and evaluate its impact on visual quality. Micrometer ultra-high resolution optical coherence tomography (OCT) enables us to quantify thickness and volume of the tear over the cornea and tear menisci. The ocular surface imaging ellipsometer uses polarized illumination from which both the lipid refractive index and thickness can be measured at a very high resolution. Using an enhanced thermal camera, we measure the ocular surface temperature noninvasively, which makes it possible to study spatial and temporal changes in tear evaporation. The multimodal deployment of these four components in the controlled chamber will assist in better differentiating the various clinical dry eye entities and will lead to the development of specific dry eye treatments.

Infectious endophthalmitis in adult eyes receiving Boston type I keratoprosthesis.

PURPOSE: To report the clinical characteristics of infectious endophthalmitis after Boston type I keratoprosthesis (K-Pro) implantation. DESIGN: Retrospective study. PARTICIPANTS: One hundred forty-one adult eyes receiving a K-Pro at a single institution from May 2004 through July 2008. METHODS: A retrospective chart review was performed of all adult eyes receiving a K-Pro at the University of Rochester from May 2004 through July 2008. Those patients identified as having been treated for exogenous bacterial endophthalmitis were reviewed for demographic data, indication for K-Pro, bandage contact lens use, prophylactic antibiotic use, timing and clinical presentation of endophthalmitis, gram stain and culture results of intraocular fluid, timing and presentation of any subsequent episodes of endophthalmitis (recurrent endophthalmitis), and preoperative and postoperative visual acuity through August 2010. MAIN OUTCOME MEASURES: Incidence of endophthalmitis, time to occurrence, recurrence rates, visual outcomes, and risk factors associated with K-Pro endophthalmitis. RESULTS: Ten (7.1%) of 141 eyes of 130 adult patients were diagnosed and treated for bacterial endophthalmitis. Average time to endophthalmitis developing after K-Pro was 9.8 months (standard deviation [SD], 6.2 months; range, 2-25 months). Coagulase-negative staphylococci were identified in 7 eyes. In 7 of the 10 eyes, recurrent endophthalmitis developed that occurred at a mean of 4 months (SD, 3.9 months; range, 1-13 months) after resolution of the initial episode. At each episode of endophthalmitis, no eye was receiving vancomycin ophthalmic drops and most eyes were receiving only fluoroquinolone ophthalmic drops for prophylaxis. CONCLUSIONS: Infectious endophthalmitis after K-Pro implantation has a higher incidence, delayed onset, and high risk for recurrence compared with postoperative endophthalmitis associated with more common intraocular procedures such as cataract surgery. The concurrent use of topical vancomycin is recommended because it seems to be important in reducing the incidence and recurrence of endophthalmitis and because fluoroquinolone ophthalmic drops do not seem to be sufficient prophylaxis in these eyes.