Purpose To describe the outcomes of limbal stem cell transplantation in eyes with limbal stem cell deficiency related to soft contact lens wear. Design Retrospective interventional case series. ...Methods Institutional database search at the Cincinnati Eye Institute revealed 9 patients (14 eyes) who underwent limbal stem cell transplantation with systemic immunosuppression for soft contact lens wear–related limbal stem cell deficiency. Outcome measures included patient demographics, symptoms, best-corrected visual acuity, ocular surface stability, adverse events, and additional surgeries required. Results Average patient age at time of surgery was 46.6 ± 11.1 years (range 20–60 years). Average duration of follow-up was 28 ± 19.1 months (range 12–70 months). Preoperative best-corrected visual acuity (BCVA) was 20/40 or worse in all eyes (average 20/70, range 20/40–20/250) and patient symptoms included foreign body sensation, tearing, redness, and/or pain. Four eyes (29%) underwent living-related conjunctival limbal allograft and 10 eyes (71%) underwent cadaver-donor keratolimbal allograft surgery. Topical and systemic immunosuppression was used in all patients. At final follow-up after limbal stem cell transplantation, there was a stable ocular surface in 12 of 14 eyes (86%) and improvement in BCVA to 20/30 or better and complete resolution of patient symptoms in all except 1 patient who had significant rosacea blepharokeratoconjunctivitis, whose BCVA remained at 20/150 and 20/60, in right and left eyes, respectively. The most common adverse event was an increase in intraocular pressure in 8 of 14 eyes (57%), requiring topical antiglaucoma treatment. Ten of 14 eyes (71%) underwent cataract extraction related to topical steroid use. No eyes required subsequent penetrating keratoplasty. Conclusion Limbal stem cell transplantation is a viable option for the management of soft contact lens wear–related limbal stem cell deficiency in young healthy patients. Early intervention prior to subepithelial fibrosis can lead to good visual outcomes with no need for subsequent cornea transplant. Co-management with a solid organ transplant specialist is helpful for the monitoring and management of systemic adverse events related to patient systemic immunosuppression.
To report our surgical experience with ocular surface stem cell transplantation (OSST) for limbal stem cell deficiency (LSCD) in the setting of keratitis-ichthyosis-deafness (KID) syndrome.
...Retrospective interventional case series.
We present 5 eyes of 3 patients with KID syndrome that developed LSCD and underwent OSST. Mean follow-up after OSST was 8.3 ± 4.3 years (range 3.4-11.4 years). Two eyes underwent living-related conjunctival limbal allograft (lr-CLAL), and 3 eyes were treated with keratolimbal allograft (KLAL). Four of the 5 eyes underwent subsequent keratoplasty. Both lr-CLAL eyes maintained a stable ocular surface at final follow-up. Conversely, all KLAL eyes developed a failed surface requiring repeat KLAL surgery. Because of multiple failed KLALs, 1 eye underwent placement of a keratoprosthesis.
KID syndrome is a rare cause of LSCD. Although OSST can stabilize the surface, long-term treatment of KID syndrome can be challenging. An lr-CLAL may offer further benefit over a KLAL in these eyes because it is HLA- and ABO-matched tissue; it also helps to treat keratoconjunctivitis sicca, often a prominent feature of KID syndrome.
To describe the clinical features and management strategies in patients whose limbal stem cell (LSC) disease reversed with medical therapy.
Retrospective case series.
Twenty-two eyes of 15 patients ...seen at 3 tertiary referral centers between 2007 and 2011 with 3 months or more of follow-up.
Medical records of patients with medically reversible LSC disease were reviewed. Demographic data, causes, location and duration of disease, and medical inventions were analyzed.
Primary outcomes assessed included resolution of signs of LSC disease and improvement in visual acuity.
Causes of the LSC disease included contact lens wear only (13 eyes), contact lens wear in the setting of ocular rosacea (3 eyes), benzalkonium chloride toxicity (2 eyes), and idiopathic (4 eyes). Ophthalmologic findings included loss of limbal architecture, a whorl-like epitheliopathy, or an opaque epithelium arising from the limbus with late fluorescein staining. The superior limbus was the most common site of involvement (95%). The corneal epithelial phenotype returned to normal with only conservative measures, including lubrication and discontinuing contact lens wear in 4 patients (4 eyes), whereas in 11 patients (18 eyes), additional interventions were required after at least 3 months of conservative therapy. Medical interventions included topical corticosteroids, topical cyclosporine, topical vitamin A, oral doxycycline, punctal occlusion, or a combination thereof. All eyes achieved a stable ocular surface over a mean follow-up of 15 months (range, 4-60 months). Visual acuity improved from a mean of 20/42 to 20/26 (P < 0.0184).
Disturbances to the LSC function, niche, or both may be reversible with medical therapy. These cases, which represent a subset of patients with LSC deficiency, may be considered to have LSC niche dysfunction.
The endothelial cell is a critical structure within the cornea and is responsible for maintaining corneal clarity through its pump function. Endothelial cells are lost over time naturally but can be ...injured medically, surgically, or as a part of various dystrophies. Monitoring of endothelial cells can be performed clinically or more formally with specular microscopy. In cases of significant compromise, endothelial cells can be transplanted by various endothelial keratoplasty techniques. The future pipeline is bright for possible endothelial cell regeneration and rehabilitation. This article reviews these topics in depth to provide a comprehensive look at the structure and function of the endothelial cell, etiologies of endothelial cell damage, detailed review of iatrogenic causes of endothelial cell loss, and management strategies.
To investigate the long-term clinical outcomes of conjunctival limbal autograft (CLAU) in patients with unilateral total limbal stem cell deficiency (LSCD).
In this retrospective interventional case ...series, the medical charts of patients with unilateral total LSCD were reviewed. Patients who underwent CLAU and no other allograft ocular stem cell transplantation with a minimum follow-up of 1 year were included. Main outcome measures were ocular surface stability, best-corrected visual acuity (BCVA), and postoperative complications.
27 eyes fulfilled the inclusion criteria with a mean follow-up period of 49.8 ± 36.6 months (4.15 years; range 12–186.72 months; 1–15.56 years). Ocular surface stability was achieved in 77.8% (n = 21) of eyes at last follow-up, while 22.2% (n = 6) developed partial surface failure. Optical penetrating or deep lamellar anterior keratoplasty was performed in 44.45% (n = 12). BCVA improved from 1.42 ± 0.95 mean LogMAR (equivalent to 20/400) preoperatively to 0.53 ± 0.47 mean LogMAR (equivalent to 20/70) at last follow-up (p < 0.001). BCVA ≥20/40 was achieved in 44.45% (n = 12) at last follow-up. Microbial keratitis occurred in 14.81% (n = 4). Ocular hypertension secondary to corticosteroid use developed in 25.9% (7/27) eyes. There were no other complications in the donor or recipient eyes.
CLAU can provide long-term ocular surface stability and successful visual outcomes in patients with unilateral LSCD.
To describe the clinical presentation and management of late (>3.0 years) acute graft rejection in keratolimbal allograft (KLAL) recipients.
This was a multicenter, retrospective observational case ...series. Six eyes of 6 patients with ocular surface transplant at a mean age of 36.2 years were seen at 3 tertiary referral centers for acute graft rejection between 2007 and 2013. Main outcome measures included strength of systemic immunosuppression (SI) at the time of rejection, time to rejection, and clinical presentation of rejection.
Preoperative diagnoses included total limbal stem cell deficiency because of aniridia (n = 2) or chemical injury (n = 4). After an initially successful outcome, patients experienced late acute graft rejection at a mean time of 67.8 ± 24.1 months (range: 41-98) after KLAL while receiving suboptimal levels of SI because of medication taper (n = 5) or noncompliance (n = 1). Objective findings included an epithelial rejection line (n = 6), edema (n = 2), corneal epithelial irregularities (n = 2), and neovascularization (n = 1). Antirejection management consisted of topical corticosteroids (n = 6) and augmentation of SI therapy (n = 5).
These cases of late acute graft rejection in KLAL patients support the notion that allodonor cells can persist over the long run and remain at risk for immunologic rejection. It further underscores the fact that long-term success with KLAL may require extension of SI beyond the first few years, albeit at lower levels individualized to each patient.
The removal and rate of recurrence of pterygium have been discussed for years. The disorder is highly associated with environmental factors, and recurrence rates can be unacceptably high and cannot ...be successfully predicted. New techniques and graft preparations and postoperative management strategies are helping to reduce the recurrence rates and provide an ocular surface that is near ideal for future cataract or refractive surgery. This review discusses the advantages and disadvantages of various treatment strategies.
We assess the safety and effectiveness of intranasal neurostimulation to promote tear production via the nasolacrimal pathway in subjects with dry eye disease.
A multicenter, randomized, controlled, ...double-masked pilot study was conducted in adults with dry eye diagnosis and at least one eye with corneal fluorescein staining ≥2 in at least one region or a sum of all regions ≥5 (National Eye Institute grading), basal Schirmer test score ≤10 mm, a cotton-swab stimulated Schirmer score ≥7 mm higher, and an Ocular Surface Disease Index score ≥23. Subjects were randomized to receive active intranasal neurostimulation or sham control intranasal stimulation 4 to 8 times per day. Assessments were scheduled before (unstimulated) and during (stimulated) device application at days 0, 7, 14, 30, and 90. The primary effectiveness endpoint was stimulation-induced change in Schirmer test (with anesthesia) score. Primary safety measure was incidence of device-related adverse events (AEs).
Fifty-eight subjects were randomized at nine sites in Australia and New Zealand; 56 completed the 90-day study. Stimulation-induced change in Schirmer score was significantly greater with active intranasal (mean ± SEM, 9.0 ± 2.0) than sham control intranasal stimulation (0.4 ± 0.6; P < 0.001) at day 90. Similar results were observed at days 0, 7, 14, and 30 (P < 0.001). No serious device-related AEs were observed. Mild nosebleed, the most common device-related AE, was reported in five (16.7%) subjects.
Intranasal neurostimulation was effective in inducing acute tear production after 90 days of use and generally was well tolerated in subjects with dry eye disease.
The optimal treatment and management of locally advanced pancreatic cancer (LAPC) remains unclear and controversial. This study aimed to report the initial outcomes of the AHPBA Registry and evaluate ...the reproducibility of existing evidence that the addition of Irreversible Electroporation (IRE), a nonthermal ablative treatment, confers survival benefits beyond standard therapeutic options for patients with LAPC.
From December 2015 to October 2017, patients with LAPC were treated with open-technique IRE following the AHPBA Registry Protocols. Patient demographics, long-term outcomes, and adverse events were recorded. Survival analyses were performed using Kaplan-Meier (KM) curves for overall survival (OS), progression free survival (PFS) and time to progression (TTP).
A total of 152 patients underwent successful IRE. Morbidity and mortality were 18% and 2% respectively, with 19 (13%) patients experiencing severe adverse events. Nine (6%) patients presented with local recurrence. Median TTP, PFS, and OS from diagnosis were 27.3 months, 22.8 months, and 30.7 months respectively.
The combination of IRE with established multiagent therapy is safe and demonstrates encouraging survival among patients with LAPC. IRE is associated with a low rate of serious adverse events and has been optimized for more widespread adoption through the standardized protocols available through the AHPBA registry.
The aim of this study was to characterize the outcomes of eyes with neurotrophic keratitis (NK) treated with a course of cenegermin-bkbj in the presence of a bandage contact lens (BCL).
A ...retrospective chart review of all eyes with a clinical diagnosis of NK treated with cenegermin-bkbj was performed between 2018 and 2020. Inclusion criteria included cenegermin-bkbj treatment with a BCL in place. Demographics, etiology, visual acuity, pretreatment and posttreatment corneal sensation, and treatment outcomes were assessed.
There were 18 eyes of 16 patients (69% female) with NK treated with cenegermin-bkbj while having a BCL in place. After cenegermin-bkbj treatment, presence of corneal sensation significantly increased from 7% of eyes to 79% of eyes (P < 0.0001). There was also a significant increase in the number of quadrants with corneal sensation (mean of 0.1 quadrants increased to 1.6 quadrants, P =0.0005). Six of 10 eyes (67%; P = 0.004) with a persistent epithelial defect (PED) experienced complete resolution at the conclusion of treatment, while 3 additional eyes experienced a decrease in the defect size. Despite all 18 eyes necessitating a chronic BCL before cenegermin-bkbj treatment, 4 were able to maintain their epithelium without a BCL after treatment for at least some period.
Cenegermin-bkbj treatment for NK with a BCL in place demonstrated improvement in corneal sensation, epithelial defect size, and fluorescein staining. In eyes demonstrating previous ocular surface decompensation with discontinuation of a BCL, maintenance of BCL use during treatment with cenegermin-bkbj may be considered.
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