Metalloproteinase-9 in the ocular surface of patients with implanted Boston type 1 keratoprosthesis.

PURPOSE: To characterize the presence of ocular surface inflammation, using matrix metalloproteinase 9 (MMP-9) as a marker, in the ocular surface of eyes with implanted Boston Keratoprosthesis type 1 (KPro). METHODS: Patients with implanted KPro at a single tertiary center were recruited to assess ocular inflammation. MMP-9 was measured using InflammaDry® test in both eyes of each patient. The non-KPro eye served as control. Rate of positivity of MMP-9 was compared between groups. Possible associations between ocular surface inflammation and the development of postoperative complications were evaluated using univariate statistical analysis. RESULTS: Fifty eyes from 25 patients were included. The mean age was 50 years old. Non-inflammatory indications for KPro were predominant among patients. Eighty eight percent of KPro eyes had a positive test for MMP-9 while only 25% of control eyes were positive (p<001). The most common complications were retroprosthetic membrane, epithelial defects, and sterile corneal melt. The presence of a strong positive result was associated to a higher frequency of complications (80% of eyes) compared to a faint positive test (54%) and a negative test (33%). CONCLUSION: The KPro device appears to increase MMP-9 levels in the ocular surface. High MMP-9 levels may be associated with higher risk of complications. MMP-9 testing can be useful to assess subclinical ocular surface inflammation with a potential role in the postoperative care of KPro patients.

Pediatric Phlyctenular Keratoconjunctivitis at a Tertiary Care Center in the United States.

PURPOSE: The aim of this study was to evaluate characteristics and outcomes of pediatric phlyctenulosis at a tertiary care center in the United States. METHODS: A retrospective cohort study of phlyctenulosis diagnosis in patients younger than 18 years was conducted. Demographics, presenting features, treatment regimens, and outcomes were analyzed. RESULTS: Seventy patients (95 eyes) with phlyctenulosis were identified. Fifty-four patients (77.1%) were Hispanic, which was greater than the center's proportion of pediatric patients identifying as Hispanic (53.8%, P < 0.0001). Common comorbidities included adjacent external/lid disease (82.9%), allergic/atopic disease (18.6%), and viral infections (8.6%). Nine patients had tuberculosis testing which was negative in all cases. Five patients had vitamin A testing which revealed deficiency in 1 patient. Treatment regimens were diverse and included varying combinations of topical and systemic medications. Complications included corneal scarring (27.4%), corneal neovascularization (40.0%), amblyopia (16.8%), corneal perforation (3.2%), and severe limbal stem-cell deficiency (1.1%). 26.3% of affected eyes had final visual acuity worse than 20/40. Differences in rates of corneal complications between Hispanic and non-Hispanic patients were not statistically significant, although severe corneal complications including perforation occurred only in the Hispanic group. CONCLUSIONS: This study presents a modern cohort of phlyctenulosis at a tertiary center in the United States and includes a larger proportion of Hispanic patients than expected. Phlyctenulosis carries high corneal morbidity and may frequently result in reduced visual acuity. Similar rates of corneal complications were seen in Hispanic versus non-Hispanic patients, but severe corneal complications were seen only in the Hispanic group.

Visual Rehabilitation With Contact Lenses Following Open Globe Trauma.

OBJECTIVES: To describe visual outcomes with various contact lens modalities in patients with a history of ocular trauma who underwent surgical open globe repair. METHODS: Records of all patients with a history of open globe injury and repair at a tertiary care hospital between January 1, 2010, and December 31, 2016, were reviewed. Demographics, type of injury, and visual acuity were assessed before and after contact lens evaluation. RESULTS: Of 214 patients who underwent open globe repair, 29 (13.6%) were evaluated with a contact lens. Visual acuity improved in 97% (28 of 29) of patients from 1.47±0.75 to 0.67±0.71 logarithm of the minimal angle of resolution (logMAR) with manifest refraction to 0.28±0.45 logMAR with contact lenses (n=29; P<0.0001). Corneal opacity was the most common clinical indication (20 of 29) for fitting followed by aphakia (13 of 29). A range of contact lens modalities, including corneal rigid gas-permeable (12 of 28), soft (9 of 28), hybrid (3 of 28), scleral gas-permeable (2 of 28), and piggyback (2 of 28) lenses were prescribed. CONCLUSION: In this study, patients with a history of trauma and open globe repair with good neurosensory visual potential had improvements in visual acuity with contact lens greater than manifest refraction. Soft and gas-permeable lenses were used to improve visual acuity in patients with a history of open globe repair and corneal scarring, aphakia, iris abnormalities, or other ocular sequelae. Although corneal rigid gas-permeable lenses were prescribed most often, additional consideration should be given to other contact lens modalities, including soft, piggyback, hybrid, and scleral gas-permeable lenses.

Boston Type 1 Keratoprosthesis: Updated Perspectives.

The use of Boston type 1 keratoprosthesis (BKPro) has significantly increased worldwide. It is no longer considered a procedure of last resort but a reasonable option for patients with otherwise poor prognosis for a traditional penetrating keratoplasty. BKPro was approved by the Food and Drug Administration in 1992 for bilateral severe corneal blindness due to multiple corneal transplant failure. Over the years, indications have extended beyond recurrent immunologic rejection to include other conditions such as chemical injury and other causes of bilateral limbal stem cell deficiency, extensive corneal neovascularization, neurotrophic corneas and hypotony, among others. Numerous advances in the design of the BKPro, improvement of preoperative, intraoperative and postoperative management have resulted in favorable outcomes and a reduction in postoperative complications. Accordingly, many studies have shown that implantation of this device is highly effective in restoring vision with very good short-term outcomes. However, due to the lifetime risk of sight-threatening complications after BKPro implantation, a longer follow-up period should provide outcomes that are more realistic. In this review, the authors examined only the results of publications with an average of at least 2 years of follow-up. The overall intermediate to long-term visual outcomes and retention rate in BKPro seem to be favorable. However, autoimmune diseases and cicatrizing conditions continue to show a higher incidence of postoperative complications that require further management.

Transgenic models for investigating the nervous system: Currently available neurofluorescent reporters and potential neuronal markers.

Recombinant DNA technologies have enabled the development of transgenic animal models for use in studying a myriad of diseases and biological states. By placing fluorescent reporters under the direct regulation of the promoter region of specific marker proteins, these models can localize and characterize very specific cell types. One important application of transgenic species is the study of the cytoarchitecture of the nervous system. Neurofluorescent reporters can be used to study the structural patterns of nerves in the central or peripheral nervous system in vivo, as well as phenomena involving embryologic or adult neurogenesis, injury, degeneration, and recovery. Furthermore, crucial molecular factors can also be screened via the transgenic approach, which may eventually play a major role in the development of therapeutic strategies against diseases like Alzheimer's or Parkinson's. This review describes currently available reporters and their uses in the literature as well as potential neural markers that can be leveraged to create additional, robust transgenic models for future studies.

Recognition of Fungal Keratitis in Boston Type I Keratoprosthesis: Importance of Awareness and Novel Identification of Exophiala phaeomuriformis.

PURPOSE: To present a case of Exophiala phaeomuriformis fungal keratitis to demonstrate the heightened concern for fungal infection in patients with a keratoprosthesis and to highlight the rare involvement of Exophiala phaeomuriformis. METHODS: Case report. RESULTS: Exophiala phaeomuriformis was identified in a susceptible patient 7 years after Boston type I keratoprosthesis (KPro) implantation. CONCLUSIONS: Although fungal infiltration after KPro placement does not represent a novel clinical infection, identification of the rare Exophiala species in a patient with a KPro has not been reported and provides an opportunity for reflection on fungal identification, prophylaxis, and prevention in this vulnerable patient population.

Assessment of Glaucomatous Damage After Boston Keratoprosthesis Implantation Based on Digital Planimetric Quantification of Visual Fields and Optic Nerve Head Imaging.

PURPOSE: To investigate glaucomatous damage in Boston keratoprosthesis type I (KPro) patients through structural analysis of the optic nerve head and digital planimetric quantification of Goldmann visual fields, a novel method of monitoring perimetric changes in KPro patients. METHODS: Records of patients undergoing KPro implantation from 2007 to 2015 at a single institution were reviewed. Parameters related to glaucoma status and KPro outcomes were analyzed. RESULTS: Twenty-two eyes from 21 patients met inclusion criteria, with mean follow-up of 49.4 months (range 15-90). Mean results for the following parameters before KPro implantation and at last follow-up were (pre-KPro; at last follow-up): best-corrected visual acuity (2.07; 0.70 logMAR), number of glaucoma medications (1.14; 1.05), intraocular pressure (IOP) (18.4; 18.4 mm Hg), vertical cup-to-disc ratio (C/D) (0.48; 0.50), and horizontal C/D (0.52; 0.52). IOP-lowering procedures were performed pre-KPro (5/22), concurrently with KPro (10/22), post-KPro (6/22), or never (6/22). An increase in C/D ≥0.1 and loss of V4e isopter area >30% occurred in 22.7% and 12.5%, respectively. Development of post-KPro glaucoma, progression of preexisting or post-KPro glaucoma, and no glaucoma development as evidenced by an objective assessment of structural and functional parameters were seen in 2/22 (9.1%), 7/22 (31.8%), and 6/22 (27.3%) eyes, respectively. CONCLUSIONS: Clinicians should strive to vigilantly monitor for glaucoma despite the inherent difficulties in tonometry, optic nerve visualization and imaging, and visual field testing in KPro patients. Meticulous glaucoma surveillance with structural and functional testing combined with earlier IOP-lowering surgical intervention may result in decreased rates of glaucomatous vision loss in KPro patients.

Angiogenesis and lymphangiogenesis in corneal transplantation-A review.

Corneal transplantation has been proven effective for returning the gift of sight to those affected by corneal disorders such as opacity, injury, and infections that are a leading cause of blindness. Immune privilege plays an important role in the success of corneal transplantation procedures; however, immune rejection reactions do occur, and they, in conjunction with a shortage of corneal donor tissue, continue to pose major challenges. Corneal immune privilege is important to the success of corneal transplantation and closely related to the avascular nature of the cornea. Corneal avascularity may be disrupted by the processes of angiogenesis and lymphangiogenesis, and for this reason, these phenomena have been a focus of research in recent years. Through this research, therapies addressing certain rejection reactions related to angiogenesis have been developed and implemented. Corneal donor tissue shortages also have been addressed by the development of new materials to replace the human donor cornea. These advancements, along with other improvements in the corneal transplantation procedure, have contributed to an improved success rate for corneal transplantation. We summarize recent developments and improvements in corneal transplantation, including the current understanding of angiogenesis mechanisms, the anti-angiogenic and anti-lymphangiogenic factors identified to date, and the new materials being used. Additionally, we discuss future directions for research in corneal transplantation.

Histopathological and immunohistochemical analysis of melt-associated retroprosthetic membranes in the Boston type 1 keratoprosthesis.

IMPORTANCE: Retroprosthetic membrane (RPM) formation is the most common complication associated with the Boston type 1 keratoprosthesis and has been associated with corneal melt. OBJECTIVE: To identify the histological and immunohistochemical characteristics of RPMs associated with corneal melt. DESIGN, SETTING, AND PARTICIPANTS: Observational histopathological case series at a tertiary eye care referral center among patients who underwent Boston type 1 keratoprosthesis explantation because of donor corneal melt at the Illinois Eye and Ear Infirmary between January 1, 2011, and January 1, 2012. EXPOSURES: Seven RPM specimens from 7 eyes were stained with hematoxylin-eosin, cytokeratin 7, cytokeratin AE1/3, smooth muscle actin, vimentin, and CD34. Light microscopy was used to evaluate specimens for inflammation and epithelial ingrowth. XY-karyotyping using fluorescence in situ hybridization was performed on 4 specimens with known donor-recipient sex mismatch. MAIN OUTCOMES AND MEASURES: Histological and immunohistochemical characteristics of RPMs. RESULTS: Inflammatory cells were present in 4 of 7 RPMs. In 3 of 4 sex-mismatched specimens, tissue XY-karyotyping of the RPM interphase cells was consistent with the host sex karyotype. The fourth specimen showed a mixture of recipient-type and donor-type cells. CONCLUSIONS AND RELEVANCE: Melt-associated RPMs show variable degrees of inflammation. Most membranes seem to originate from a proliferation of host cells, but donor tissue may contribute in some cases.

Correction: Anterior Segment Optical Coherence Tomography for the Quantitative Evaluation of the Anterior Segment Following Boston Keratoprosthesis.

[This corrects the article on p. e70673 in vol. 8.].

Anterior segment optical coherence tomography for the quantitative evaluation of the anterior segment following Boston keratoprosthesis.

OBJECTIVE: To quantitatively evaluate the anterior segment using anterior segment optical coherence tomography (AS-OCT) following Boston keratoprosthesis type 1. METHODS: A retrospective study consisted of AS-OCT imaging at a single time point postoperatively in 52 eyes. Main outcomes measures include anatomical and functional anterior chamber depth (ACD), angle (ACA) and peripheral and proximal synechiae. RESULTS: The mean time point of imaging was 19.3 months postoperatively. Average anatomical and functional ACD was 2.0 and 0.21 mm respectively, and mean ACA ranged from 2.5° to 6.14° in representative meridians. An average of 8.7 clock hours of angle closure was observed in the 25 eyes in which all meridians were imaged. The majority of eyes showed peripheral (86.5%) and proximal (67.3%) synechiae. CONCLUSIONS: AS-OCT is a useful tool for quantitative evaluation of anterior segment and angle after keratoprosthesis, which is otherwise poorly visible. The majority of eyes showed shallow ACD, extensive angle closure and synechiae formation.

Serial Analysis of Anterior Chamber Depth and Angle Status Using Anterior Segment Optical Coherence Tomography After Boston Keratoprosthesis.

PURPOSE: To analyze iris behavior and angle status using serial anterior segment optical coherence tomography (AS-OCT) after Boston keratoprosthesis (KPro). METHODS: A prospective cases series consisted of 11 eyes with implanted type 1 KPro at a tertiary care institution. The patients underwent preoperative and serial postoperative AS-OCT imaging. The main outcome measures included anterior chamber angle (ACA) at representative meridians (0 degrees, 45 degrees, 90 degrees, 135 degrees, 180 degrees, 225 degrees, 270 degrees, and 315 degrees), grading of total ACA as open (>10 degrees), shallow (≥1 degrees and ≤10 degrees) or closed (<1 degrees), preoperative anterior chamber depth (ACD), postoperative anatomical and functional ACD, and the presence of iris-back plate touch and peripheral anterior synechiae. RESULTS: The mean follow-up with serial AS-OCT was 13.1 months. Preoperatively, 54.5%, 27.3%, and 18.2% of the eyes had open, shallow, and closed angles, respectively. The mean change in the effective ACD decreased postoperatively by 1.61 mm. At 0 degree and 180 degree meridians, the ACA decreased by a mean change of 6.95 degrees and 8.40 degrees, with a mean change of 8.12 degrees for all meridians. Eight (72.7%) eyes had synechiae with 7.3 and 6.7 clock hours of peripheral anterior synechiae and iris-back plate touch. At the last follow-up, 7 (63.6%) eyes had considerable progression of angle closure (change in grading of total angle), and 18.2%, 36.4%, and 45.5% had open, shallow, and closed angles, respectively. CONCLUSIONS: KPro implantation induced progressive angle closure, shallowing of the anterior chamber, and synechiae formation that is not visible on clinical examination. Serial AS-OCT plays an important role in the detection and monitoring of progressive angle closure, and clinical correlation is needed to assess the association with glaucoma development or progression.

Use of a porous polyethylene lid spacer for management of eyelid retraction in patients with Boston type II keratoprosthesis.

PURPOSE: To report a novel application of a porous polyethylene implant for lid stabilization and management of eyelid retraction in a patient with an exposed Boston Keratoprosthesis Type II. METHODS: A 54-year-old woman with a history of mucous membrane pemphigoid and failed penetrating keratoplasty of the left eye underwent implantation of a Boston Keratoprosthesis (KPro) Type II along with permanent surgical fusion of the upper and lower lids of the left eye in January 2010. At one month follow-up, significant retraction of the lower lid around the inferior margin of the optic was noted, resulting in partial exposure of the keratoprosthesis. The patient subsequently underwent left lower eyelid reconstruction with a porous polyethylene implant to ensure coverage and stability of the KPro. RESULTS: Eyelid reconstruction using a porous polyethylene implant resulted in stable retention of the KPro Type II for over 2 years. CONCLUSION: In patients with Boston KPro Type II in the setting of severe cicatrizing ocular surface disease, the use of a porous polyethylene implant during eyelid reconstruction around the KPro optic may aid in maintaining eyelid integrity and improving KPro stability and longevity.

Neuroprotectin D1 restores corneal nerve integrity and function after damage from experimental surgery.

PURPOSE: To investigate if topical treatment of neuroprotectin D1 (NPD1) increases regeneration of functional nerves after lamellar keratectomy. METHODS: An 8-mm stromal dissection was performed in the left eye of each rabbit. The rabbits were treated with NPD1, pigment epithelial-derived factor (PEDF) in combination with docosahexaenoic acid (DHA) or vehicle for 6 weeks, and corneas were obtained at 8 weeks. After fixation, corneal wholemounts were stained with mouse monoclonal anti-ßIII-tubulin antibody and double stained with chicken anti-calcitonin gene-related peptide (CGRP) antibody. Corneal sensitivity and tear secretion were measured using the Cochet-Bonnet esthesiometer and the Schirmer's test, respectively. Additional rabbits were treated with NPD1, PEDF+DHA, or vehicle, and corneal sections were stained with a rat monoclonal anti-neutrophil antibody. Cultures of trigeminal ganglia from 5-day-old mice were treated with NPD1, PEDF+DHA, lipoxin A4 (LXA4), 12- or 15-hydroxyeicosatetraenoic acid (12[S] or 15[S]-HETE), and nerve growth factor (NGF) as positive control. RESULTS: NPD1 increased subepithelial corneal nerve area three times compared with vehicle-treated rabbits. The effect was similar to PEDF+DHA-treated animals. There was recovery of CGRP-positive neurons and an increase in corneal sensitivity and tear secretion in NPD1-treated animals. NPD1 decreased neutrophil infiltration after 2 and 4 days of treatment. In the in vitro cultures, NPD1 and PEDF+DHA induced a 3-fold increase in neurite outgrowth compared with cultures without supplementation. Treatments with LXA4, 12(S)-, and 15(S)- HETE did not stimulate neurite outgrowth. CONCLUSIONS: NPD1 has anti-inflammatory and nerve regenerative properties. This study demonstrates that NPD1 may offer an effective treatment for neurotrophic corneas.

Argon laser iridoplasty for optic obstruction of Boston keratoprosthesis.

The Boston keratoprosthesis (KPro) has been used successfully in eyes with poor prognosis for conventional penetrating keratoplasty. However, postoperative changes in iris configuration after Boston KPro may occur, including iris obstruction of the Boston KPro, limiting visual potential in otherwise successful transplants. We describe our technique of argon laser iridoplasty after Boston KPro as a safe and effective procedure to treat visually significant optic obstruction and as a less-invasive alternative to surgical intervention.

Visual outcomes of Boston keratoprosthesis implantation as the primary penetrating corneal procedure.

PURPOSE: To report the short-term visual outcomes and complications of keratoprosthesis surgery as the primary penetrating corneal procedure for patients at high risk for conventional corneal transplantation. METHODS: A retrospective chart review was conducted of 21 eyes of 19 patients who underwent either Boston keratoprosthesis type I or type II as the primary penetrating corneal procedure from February 2007 to March 2011. RESULTS: Nineteen type I (90.5%) and 2 type II (9.5%) Boston keratoprosthesis procedures were performed in 19 patients. Mean follow-up was 14.6 months (range, 6-36.3 mo). Primary indications for surgery included chemical or thermal injury, aniridia, and Stevens-Johnson syndrome. Preoperative best-corrected visual acuity (BCVA) ranged from 20/100 to light perception and was count fingers or worse in 20 eyes (95.2%). At last follow-up for all eyes, 15 eyes (71.4%) achieved BCVA≥20/200 and 4 eyes (19%) improved to BCVA≥20/50. No intraoperative complications occurred. Postoperative complications include retroprosthetic membrane formation (47.6%), cystoid macular edema (33.3%), elevated intraocular pressure (23.8%), glaucoma progression (14.3%), and endophthalmitis (4.8%). The initial keratoprosthesis was retained in 19 eyes (90.5%). CONCLUSION: The Boston keratoprosthesis, based on early follow-up, is a good alternative as a primary penetrating corneal procedure in a select group of patients with very poor prognosis for penetrating keratoplasty. Although complications can occur and require close monitoring, visual acuity significantly improved in the majority of patients.