Combined Corneal Transplant, Glaucoma Drainage Implantation, and Pars Plana Vitrectomy Outcomes in a Pediatric Population.

PURPOSE: The combination of glaucoma drainage device (GDI), pars plana vitrectomy (PPV), and corneal transplantation is well reported in adults. However, little is known about the outcomes of such combined procedures in pediatric patients. We present a retrospective, single-center study to evaluate the safety and outcomes of concurrent GDI and/or PPV with corneal transplantation in patients 18 years and younger. METHODS: Retrospective chart review of pediatric patients (aged 0-18 years) who received either corneal transplants or keratoprosthesis in combination with at least 1 additional procedure (either GDI and/or PPV) at the Illinois Eye and Ear Infirmary, Chicago, IL, between 2003 and 2017. Primary outcomes included vision, intraocular pressure, and cup-to-disc ratio (C/D). Secondary outcomes included the number of repeat surgeries and intraoperative and postoperative complications. RESULTS: Thirty-six patients were included with a mean age of 8.4 years and an average follow-up of 49.7 months. Nineteen patients received corneal surgery, GDI, and PPV; 4 received corneal and GDI surgery; and 13 received corneal and PPV surgery. Of the 19 patients with all 3 procedures, 48% experienced an increase in vision with an average improvement of 0.9 lines at the last follow-up. Intraocular pressure decreased by an average of -7.2 mm Hg for all groups. Fifty-three percent of all patients experienced complications. CONCLUSIONS: Combined keratoplasty, GDI, and PPV seems to be effective in the management of complex pediatric eye disease. However, owing to the high risk of complications in this vulnerable patient population, careful consideration must be taken when determining a patient's surgical candidacy for combined cornea/glaucoma/retina procedures.

Corneal neurotization for neurotrophic keratopathy: Review of surgical techniques and outcomes.

Neurotrophic keratopathy is a degenerative disease in which damage to the corneal nerves leads to corneal hypoesthesia. Injuries to neurotrophic corneas are notoriously difficult to treat and have traditionally been approached with supportive management. However, recent progress in the field of corneal neurotization has given new direction for addressing nerve loss directly by stimulating new nerve growth onto the cornea from nearby sensory nerves transferred to the perilimbal region. Herein, we review the surgical techniques utilized in corneal neurotization, including direct transfers and the use of nerve grafts. Considerations in surgical approach, as well as factors that influence prognosis and outcomes of the surgical intervention are also discussed.

Retroprosthetic membrane: A complication of keratoprosthesis with broad consequences.

Keratoprosthesis (KPro) devices have the remarkable ability to restore vision in patients suffering from corneal blindness who are poor candidates for traditional penetrating keratoplasty. However, eyes with KPro can experience various complications, including the development of retroprosthetic membrane (RPM). RPMs reduce visual acuity in patients due to physical obstruction of the visual axis, but studies have shown that RPM can also lead to a variety of other consequences, from melting of the corneal carrier graft to precipitating retinal detachments. Histopathologic studies have shown that RPMs are composed of elements from both the recipient and donor. The presence of myofibroblasts in RPMs imparts them with contractile properties, which can contribute to their downstream complications, including angle closure, hypotony, and retinal detachment. At present, there are limited treatments to combat the growth of RPM. Future therapies could include anti-metabolites and targeted anti-inflammatory treatments, as well as device coatings or textured device surfaces that can hinder RPM proliferation. The long-term success of KPro depends on devising an effective solution for preventing RPM growth.

Femtosecond laser - Assisted cataract surgery in pediatric pyramidal anterior polar cataract.

PURPOSE: The purpose of this report is to describe the successful utilization of femtosecond laser assisted cataract surgery (FLACS) in a rare case of pyramidal anterior polar cataract in a female child. OBSERVATIONS: The patient is a 6 years old girl that presented to the cornea clinic with a unilateral pyramidal cataract that was deemed to be visually significant, and therefore required cataract extraction and intraocular lens implantation surgery. FLACS was proposed and mother consented to proceed with the surgery. The femtosecond laser technology enabled precise completion of a central capsulotomy around the protruding pyramidal capsular lesion. CONCLUSIONS AND IMPORTANCECONCLUSION: Various capsulorhexis techniques have been described and are used in pediatric cataracts including manual, can opener, vitrectorhexis, and laser, but none has become a standard. We propose the use of femtosecond laser for cataract extraction in cases of pediatric pyramidal cataracts, and hereby provide the first case report of such. The laser is a safe method for capsulorhexis construction and offers an additional advantage of intraoperative anterior segment OCT image guidance with visualization of the pyramidal lesion.

Resolution of an exposed pars plana Baerveldt shunt in a patient with a Boston keratoprosthesis type 1 without surgery.

Patients with a keratoprosthesis often develop complications including glaucoma, requiring glaucoma drainage devices. In most of these patients, glaucoma drainage devices have been shown to be safe and effective. However, occasionally, a glaucoma drainage device in the setting of a keratoprosthesis can lead to conjunctival erosion with mechanical trauma. While repeat surgical intervention may appear necessary, we report a case of a patient who had improved conjunctival erosion and glaucoma drainage device exposure after refitting of a therapeutic contact lens. Therapeutic contact lenses can be used to maintain hydration and decrease exposure while improving cosmesis and refractive error. Complications following keratoprosthesis surgery are an understudied area, particularly regarding glaucoma drainage devices, and we seek to show that careful fitting of therapeutic contact lenses may avoid the risks of repeat surgical intervention.

A Multicenter Study Evaluating the Risk Factors and Outcomes of Repeat Descemet Stripping Endothelial Keratoplasty.

PURPOSE: Descemet stripping endothelial keratoplasty (DSEK), currently the most common procedure for managing corneal endothelial dysfunction, may be repeated following DSEK failure from a variety of causes. This multicenter study reports the risk factors and outcomes of repeat DSEK. METHODS: This was an institutional review board-approved multicenter retrospective chart review of patients who underwent repeat DSEK. Twelve surgeons from 5 Midwest academic centers and 3 private practice groups participated. The Eversight Eye Bank provided clinical indication and donor graft data. We also assessed the role of the learning curve by comparing cohorts from the first and second 5-year periods. RESULTS: A total of 121 eyes from 121 patients who underwent repeat DSEK were identified. The average age of the patients was 70 ± 12 years. The most common indication for repeat DSEK was late endothelial graft failure without rejection (58%, N = 63). Average preoperative and 12-month postoperative repeat DSEK corrected distance visual acuities were 20/694 and 20/89, respectively. Visual acuity outcomes, endothelial cell density, and cell loss did not significantly vary between the 2 cohorts. Initial graft rebubble rates for the first and second cohorts were 51% and 25%. The presence of glaucoma, prior glaucoma surgery, or a history of penetrating (full thickness) keratoplasty did not significantly affect visual outcomes. The median, mean, and range of intraocular pressures before repeat DSEK were 15.0, 15.7, and 6 to 37 mm Hg, respectively. Patients with higher intraocular pressures before repeat DSEK had improved postoperative corrected distance visual acuities. CONCLUSIONS: Repeating DSEK improves vision following failed or decompensated DSEK surgery. Higher preoperative repeat DSEK IOPs were associated with improved visual outcomes, and initial graft rebubble rates, which decreased over time, were likely due to surgeon experience.

COMPARISON OF VISUAL AND ANATOMICAL OUTCOMES OF EYES UNDERGOING TYPE I BOSTON KERATOPROSTHESIS WITH COMBINATION PARS PLANA VITRECTOMY WITH EYES WITHOUT COMBINATION VITRECTOMY.

PURPOSE: To determine whether 1-year visual and anatomical results after surgery combining pars plana vitrectomy, Boston keratoprosthesis, and a glaucoma drainage device as needed are similar, better, or worse than Boston keratoprosthesis initial implantation alone. METHODS: We performed a retrospective review of adult patients undergoing Boston keratoprosthesis at our institution. Visual acuity outcomes, anatomical results, and complication rates of patients undergoing combination surgery (including pars plana vitrectomy and a posterior glaucoma drainage device) were compared with those undergoing keratoprosthesis placement alone. RESULTS: There were 70 eyes in the keratoprosthesis alone group and 55 eyes in the keratoprosthesis with pars plana vitrectomy group. Mean follow-up durations were 54.67 months in the keratoprosthesis alone group and 48.41 months in the combination group. Baseline mean Snellen equivalent visual acuities were worse for the combination group compared with the keratoprosthesis alone group (P = 0.027). Visual acuities improved postoperatively by 1 month after keratoprosthesis implantation for both groups and improved three or more lines of Snellen acuity in the majority of eyes for both groups (≥72% by 12 months). Eyes undergoing pars plana vitrectomy had lower rates of de novo (P = 0.015) and significantly lower rates of secondary procedures (P = 0.002) at 1 year. One year complications rates for retroprosthetic membrane formation, retinal detachment, hypotony, cystoid macular edema, epiretinal membrane formation, endophthalmitis, and corneal melting were similar for both groups. CONCLUSION: Compared with keratoprosthesis alone, combining keratoprosthesis with pars plana vitrectomy and a glaucoma drainage device as needed, resulted in lower rates of de novo glaucoma, lower rates of additional surgical procedures, similar visual acuity outcomes at 1 year, and did not result in higher complication rates.

Retroprosthetic Membrane Formation in Boston Keratoprosthesis: A Case-Control-Matched Comparison of Titanium Versus PMMA Backplate.

PURPOSE: Retroprosthetic membrane (RPM) formation is the most common complication after Boston type 1 keratoprosthesis (KPro) implantation. It affects visual acuity and can predispose to corneal melt. Two KPro backplate materials are available: titanium and polymethyl methacrylate (PMMA). This study investigates the influence of the KPro backplate material on visually significant RPM formation. METHODS: A retrospective case-control-matched study involving 40 patients; 20 eyes implanted with a titanium backplate KPro were case-matched with 20 eyes implanted with a PMMA backplate KPro between 2007 and 2015 with 1-year minimum follow-up. RESULTS: The mean follow-up duration was 28.1 ± 8.9 and 53.6 ± 24.3 months in the titanium and PMMA groups, respectively. At 12 months postoperatively, 7 eyes with titanium and 6 eyes with PMMA backplates developed a visually significant RPM. By the end of the study, a total of 11 eyes with titanium and 9 eyes with PMMA KPros developed a visually significant RPM. There was no statistically significant difference between both groups. Three of 11 eyes with titanium KPros that had a visually significant RPM required surgical membranectomy, whereas all eyes with PMMA KPros were successfully treated with the yttrium-aluminum-garnet laser. Recurrence of RPMs was found in 7/11 eyes in the titanium group and 2/9 eyes in the PMMA group with no statistical significance. CONCLUSIONS: Titanium backplate KPros do not significantly reduce RPM formation compared with PMMA backplate KPros in a case-control-matched setting. A larger prospective study is warranted to evaluate comparative long-term performance and guide newer designs.

PEDF plus DHA modulate inflammation and stimulate nerve regeneration after HSV-1 infection.

Herpes simplex virus type-1 (HSV-1) infection leads to impaired corneal sensation and, in severe cases, to corneal ulceration, melting and perforation. Here, we explore the potential therapeutic action of pigment epithelial-derived factor (PEDF) plus docosahexaenoic acid (DHA) on corneal inflammation and nerve regeneration following HSV-1 infection. Rabbits inoculated with 100,000 PFU/eye of HSV-1 strain 17Syn+ were treated with PEDF + DHA or vehicle. PEDF + DHA treatment resulted in a biphasic immune response with stronger infiltration of CD4+T cells, neutrophils and macrophages at 7-days post-treatment (p.t.) that was significantly decreased by 14 days, compared to the vehicle-treated group. Screening of 14 immune-related genes by q-PCR showed that treatment induced higher expression of IFN-γ and CCL20 and inhibition of IL-18 by 7 days in the cornea. PEDF + DHA-treated animals developed less dendritic corneal lesions, opacity and neovascularization. Corneal nerve density increased at 12-weeks p.t. with functional recovery of corneal sensation. Treatment with PEDF + DHA that was postponed by 3 weeks also showed increased nerve density when compared to vehicle. Our data demonstrate that PEDF + DHA promotes resolution of the inflammatory response to the virus and, most importantly, induces regeneration of damaged corneal nerves vital for maintaining ocular surface homeostasis.

Boston type 1 keratoprosthesis from patient selection through postoperative management: a review for the keratoprosthetic surgeon.

For the anterior segment surgeon, the implantation of Boston type 1 keratoprosthesis is a multistep process that begins with careful patient selection. Success depends on thorough preoperative evaluation, detailed surgical planning, and frequent postoperative follow-up. New practice patterns have emerged for each of these phases as the international experience with keratoprosthesis grows. This review details special considerations that can improve outcomes and also allow surgeons to consider its use in challenging patient populations at each step.

Scanning Electron Microscopic Analysis of Biofilm Formation in Explanted Human Boston Type I Keratoprostheses.

PURPOSE: To describe the morphological distribution of host tissue and microbial biofilms on the intraocular surfaces of Boston type I keratoprostheses (KPros) explanted because of corneal melt. METHODS: Retrospective study of scanning electron microscopy (SEM) images from 4 explanted Boston type I KPros composed of polymethylmethacrylate and titanium. SEM images of KPro-associated ocular surfaces were reviewed for the presence of inflammatory cells, microbes, and/or biofilm formation. One sterile type I KPro was also imaged to serve as a (device only) control. RESULTS: All 4 KPros were explanted because of culture-negative, clinically "sterile" donor corneal melt with impending KPro extrusion. In all cases, the rough, irregular surfaces of the device harbored more adherent corneal epithelium and stromacytes, inflammatory cells, and bacteria than the smooth, polished surface of the KPro optic. Two KPros showed not only evidence of prior bacterial colonization but marked biofilm formation. CONCLUSIONS: SEM images of explanted KPros explanted for "sterile" corneal melt demonstrated evidence of biofilm formation despite negative donor corneal cultures and the absence of clinical suspicion for infection. These results suggest that "sterile" corneal melt may be due to inflammatory host responses to low microbial burdens as seen in biofilms and/or released antigens after antibiotic-induced lysis. There was increased adherence of host tissue cells and microbial biofilms on the nonpolished surfaces of the KPro. Polishing the intraocular polymethylmethacrylate and titanium KPro surfaces may decrease microbial adhesion and biofilm formation in human subjects with KPros, but what impact this will have on rates of postoperative endophthalmitis is unknown.

Innovative approaches to glaucoma management of Boston keratoprosthesis type 1.

Glaucoma remains a prevalent disorder and visual limiting factor after Boston keratoprosthesis type 1 implantation. Patients with glaucoma have worse initial and late visual acuity outcomes after otherwise successful keratoprosthesis implantation. Management of glaucoma in the setting of a keratoprosthesis is challenging because of relatively rapid progression and an inability to accurately measure intraocular pressure (IOP). In addition, there are no standard guidelines for glaucoma surveillance and monitoring after keratoprosthesis surgery. This report provides a review of the current literature and offers innovative strategies that will overcome the challenges in managing glaucoma in the setting of a Boston keratoprosthesis type 1 implant. The topics that will be discussed in this section include alternative methods for IOP measurement, rationales and surgical techniques for a pars plana tube placement for glaucoma drainage device, effective medical and laser treatment, the risk for IOP elevations after YAG laser, and practical guides to glaucoma surveillance and monitoring.

The PEDF Neuroprotective Domain Plus DHA Induces Corneal Nerve Regeneration After Experimental Surgery.

PURPOSE: To compare a 44-mer pigment epithelial-derived factor (PEDF) peptide with neurotrophic activity, and a 34-mer PEDF with antiangiogenic properties in association with docosahexaenoic acid (DHA) in corneal nerve regeneration after experimental surgery. METHODS: A corneal stromal dissection was performed in rabbits. Treatment groups received topical 44-mer, 34-mer, or full PEDF plus DHA. Corneal sensitivity and Schirmer's test were performed weekly. Rabbits were euthanized at 2 and 4 days and 8 weeks. Two- and 4-day samples were stained for neutrophils and CD11b+ cells. Corneal nerves were stained with ßIII tubulin and calcitonin gene-related peptide (CGRP) antibodies in specimens collected at 8 weeks. Subepithelial nerve plexus density was calculated. A PEDF-receptor (PEDF-R) was analyzed in rabbit corneal epithelial cells (RCEC) by Western blot and immunofluorescence. RESULTS: Infiltration of CD11b+cells and neutrophils was reduced by treatment with 44-mer PEDF+DHA. A 3-fold increase in subepithelial corneal nerves and CGRP-positive nerves was found in the 44-mer PEDF+DHA-treated group compared with the 34-mer PEDF+DHA- and vehicle-treated groups. There was a 75% recovery of corneal sensitivity by week 7, and Schirmer's test reached control values in the 44-mer PEDF+DHA-treated corneas at 7 weeks. A PEDF-R protein with homology to calcium-independent phospholipase A2ς was expressed in RCEC. CONCLUSIONS: The 44-mer PEDF+DHA, but not the 34-mer PEDF+DHA, promotes functional regeneration of damaged corneal nerves. Forty four-mer PEDF, by activating a corneal epithelial receptor, in conjunction with DHA could be a novel therapeutic agent for the treatment of neurotrophic keratitis and dry eye that develops as a result of corneal nerve damage.

Contact Lens Use in Patients With Boston Keratoprosthesis Type 1: Fitting, Management, and Complications.

The Boston type 1 keratoprosthesis (KPro) is the most commonly used artificial cornea worldwide. Long-term bandage contact lenses are the standard of care for patients with these devices. The goal of bandage contact lenses is to maintain hydration and to protect the corneal tissue that surrounds the anterior plate of the keratoprosthesis which is vulnerable to desiccation, epithelial breakdown, dellen formation, and corneal melt. Contact lenses can also improve comfort, correct refractive errors, and improve the cosmesis of patients with artificial corneas. However, the continuous use of contact lenses places these patients at risk for complications such as lens loss, lens deposits, chronic conjunctivitis, and infection. In addition, obtaining an adequate fit in a patient with a compromised ocular surface and history of multiple surgeries including glaucoma drainage devices can present a challenge. This review discusses the types of contact lenses used, special fitting considerations, and common complications in patients with previous KPro surgery.

Retroprosthetic membrane and risk of sterile keratolysis in patients with type I Boston Keratoprosthesis.

PURPOSE: To evaluate whether retro-backplate retroprosthetic membrane is correlated with risk of melt in patients with a type I Boston Keratoprosthesis (KPro). DESIGN: Retrospective, observational case series. METHODS: Study of 50 eyes of 47 patients with type I Boston KPro and postoperative anterior segment optical coherence tomography (AS OCT) imaging performed at the University of Illinois at Chicago. Main outcome measures were presence of retro-backplate membrane and development of melt requiring explantation. For eyes with melt, membrane thickness was measured using the AS OCT images obtained at the last visit before melt occurred. For eyes without melt, the last available AS OCT images were used for measurement. RESULTS: AS OCT evidence of a retro-backplate membrane was observed in 100% of eyes that melted and in 34.1% of eyes that did not (P = .0034; risk ratio, 2.9; 95% confidence interval, 1.9 to 4.4). Retro-backplate membrane thickness in the melt group was 278 µm versus 193 µm in the nonmelt group (P = .025). CONCLUSIONS: The retro-backplate portion of a retroprosthetic membrane is to be differentiated from the retro-optic portion seen at the slit lamp. The retro-backplate membrane as shown by AS OCT imaging is correlated with an increased risk of sterile keratolysis, possibly because of impedance of nutritional support from the aqueous humor. Further studies are needed to better standardize the AS OCT measurements of retro-backplate membranes as well as to identify early interventions to prevent progression of thin membranes once identified on AS OCT.

Boston type I keratoprosthesis for visual rehabilitation in a patient with gelatinous drop-like corneal dystrophy.

PURPOSE: To report the use of a Boston type I keratoprosthesis as a primary penetrating procedure to treat gelatinous drop-like corneal dystrophy (GDLD), with presentation of pathologic findings and discussion of other surgical options. CASE REPORT: A 49-year-old woman with GDLD in both eyes and history of recurrent corneal opacification following multiple superficial keratectomies is presented. Best corrected visual acuity (BCVA) was counting fingers in both eyes. A Boston type I keratoprosthesis was implanted in her left eye after optical iridectomy, extracapsular cataract extraction, and anterior vitrectomy. RESULTS: The surgery was uneventful and one month after surgery, best corrected vision improved to 20/20 and has been maintained for a period of more than 14 months. No post-operative complications were observed. Histopathology of the corneal specimen is presented. CONCLUSIONS: GDLD is a rare disorder of amyloid deposition. Recurrence of this condition following surgery is extremely common. Boston type I keratoprosthesis is an effective procedure for restoring vision in affected patients.

Recovery of corneal sensitivity, calcitonin gene-related peptide-positive nerves, and increased wound healing induced by pigment epithelial-derived factor plus docosahexaenoic acid after experimental surgery.

OBJECTIVE: To assess function of regenerated corneal nerves in correlation with epithelial wound healing after experimental nerve damage in rabbits treated with pigment epithelial-derived factor (PEDF) plus docosahexaenoic acid (DHA). METHODS: An 8-mm stromal dissection was performed in the right eyes of adult New Zealand rabbits. Treatment with PEDF+DHA was for 6 weeks. Corneal sensation was measured weekly by Cochet-Bonnet esthesiometer. After 8 weeks, immunofluorescence with ßIII-tubulin, calcitonin gene-related peptide, and substance P antibodies was performed to quantify nerves. Also, rabbits were treated with PEDF+DHA for 4 weeks after lamellar keratectomy, followed by 8-mm epithelial debridement and epithelial defect assessment. One week after surgery, corneas were stained with anti-Ki67 antibody to assess cell proliferation. RESULTS: Eight weeks after surgery, calcitonin gene-related peptide-positive nerve fibers in the PEDF+DHA group were similar to normal rabbit corneas but were decreased in the vehicle. Substance P was localized in the subepithelial plexus but appeared in epithelial cells after nerve injury regardless of treatment. Five weeks after surgery, an increase in corneal sensitivity occurred in the PEDF+DHA group and reached normal values by 8 weeks. Pigment epithelial-derived factor plus DHA increased epithelial wound healing after lamellar keratectomy. One week after epithelial injury, Ki67-positive cells increased in the limbal area. CONCLUSION: Pigment epithelial-derived factor plus DHA promotes regeneration of calcitonin gene-related peptide-positive corneal nerves, accelerating wound healing and return of corneal sensitivity. CLINICAL RELEVANCE: Pigment epithelial-derived factor plus DHA represents a new approach to regenerate nerves and a potential treatment for prevention of severe dry eye after surgery or diseases of the ocular surface.

Neuroprotectin D1 synthesis and corneal nerve regeneration after experimental surgery and treatment with PEDF plus DHA.

PURPOSE: This study was conducted to define whether pigment epithelial-derived growth factor (PEDF), together with docosahexaenoic acid (DHA), enhances the synthesis of neuroprotectin D1 (NPD1) and the regeneration of corneal nerves damaged after surgery. METHODS: Corneal stromal dissection was performed in the left eyes of adult New Zealand rabbits treated with DHA+PEDF, PEDF, or DHA for 6 weeks. In vivo confocal images of the corneas were obtained at 2, 4, and 8 weeks, and nerve areas were quantified. At 8 weeks after treatment, corneas were stained with tubulin betaIII antibody, and the epithelial nerve area and the sub-basal and stromal nerve plexus were quantified. At 1 week and 2 weeks after treatment, lipids were extracted from corneas, and the synthesis of NPD1 was analyzed by mass spectrometry. Epithelial cell density was quantified by confocal microscopy 8 weeks after surgery. RESULTS: In vivo confocal images at 2 and 4 weeks after surgery showed a 2.5-fold increase in corneal nerve area in PEDF+DHA-treated animals compared with control animals. Increased nerve surface areas in epithelia, subepithelia, and stroma were observed in rabbits treated for 8 weeks with PEDF+DHA. PEDF or DHA alone did not produce a significant increase. NPD1 synthesis peaked at 1 week and was four times higher in the PEDF+DHA-treated group than in the controls. CONCLUSIONS: PEDF+DHA promotes the regeneration of corneal nerves. Neurotrophin-mediated NPD1 synthesis is suggested to precede nerve regeneration by demonstration of its accumulation upon addition of DHA and PEDF at earlier time points. Therefore, this signaling mechanism upregulates corneal nerve regeneration and may be targeted in neurotrophic keratitis, dry eye after refractive surgery, and other corneal diseases.