Why Are Corneal Specialists Resistant to Treating Patients Who Have Severe Ocular Surface Disease With Limbal Stem Cell Deficiency?

PURPOSE: To highlight the paucity of surgeons performing ocular surface stem cell transplantation with systemic immunosuppression (OSSTx with SI) for limbal stem cell deficiency (LSCD) patients, suboptimal treatments for LSCD, and obstacles to adoption. METHODS: A review of the Eye Bank Association of America annual reports and the authors' case volume for OSSTx with SI was performed. Examination of the published literature on corneal surgeries, especially for LSCD, was completed. These findings were combined with our clinical observations to develop this editorial. RESULTS: Despite techniques and protocols for OSSTx with SI published more than 30 years ago for the treatment of severe bilateral LSCD, only a small number of corneal specialists have adopted these techniques. There is a paucity of attention to this population of patients, with minimal publications to advance this area of our field. We are too often referred patients with LSCD and severe ocular surface disease that have had suboptimal treatments such as penetrating keratoplasties or primary keratoprostheses. Hesitancy for adopting OSSTx with SI is likely due to a lack of exposure to these procedures during training and fear of systemic immunosuppression. Corneal surgeons are likely unaware of the safety of systemic immunosuppression with appropriate monitoring especially when comanaging these patients with an organ transplant specialist. CONCLUSION: There is a large unmet need for the treatment of corneal blindness secondary to conjunctival and LSCD. For the vast majority of patients, OSSTx should be the first surgical choice to treat these eyes. We hope major ophthalmology centers will meet this need by building programs, and groups of corneal surgeons should collaborate to create regional centers to make this treatment more accessible to help this population.

Allogeneic Ocular Surface Stem Cell Transplantation Outcomes With Decreased or No Systemic Immunosuppression in the Elderly.

PURPOSE: The aim of this study was to report outcomes after allogeneic ocular surface stem cell transplantation (OSST) for limbal stem cell deficiency in the setting of decreased or no systemic immunosuppression (SI) in the elderly. METHODS: A retrospective chart review was performed of all eyes that underwent OSST for limbal stem cell deficiency between 2005 and 2020 at CVP Physicians. Inclusion criteria included patients who were (1) at least 70 years at the time of (2) allogeneic OSST. Postoperative SI regimens were assessed. Outcome measures included improvement in visual acuity, ocular surface stability, and adverse effects. RESULTS: There were 14 eyes of 14 patients that met the inclusion criteria with mean follow-up of 3.0 (range 0.4-7.0) years. SI was run at a lower level for 6 patients, and 8 patients did not receive any SI. Nine eyes underwent keratolimbal allograft, 1 had a living-related conjunctival limbal allograft, and 4 had combined OSST. Most eyes (85.7%) attained improvement in visual acuity during their follow-up. At the last follow-up, 57.1% maintained a stable ocular surface. Six eyes developed acute rejection or late failure. Minimal adverse events were noted. CONCLUSIONS: Elderly patients administered less or no SI exhibit overall favorable outcomes after allogeneic OSST. Although not significantly different, surface stability and duration of improved vision was greater with low SI. No SI may be an option that still achieves improved vision in a high proportion for at least part of their follow-up. Decreasing SI after OSST in this population can improve quality of life while minimizing adverse effects.

Refractory Keratolimbal Allograft Rejection in Autoimmune Polyglandular Syndrome-Associated Keratopathy Treated With Intravenous Immunoglobulin.

PURPOSE: The aim of this study was to describe the use of intravenous immunoglobulin (IVIG) in the management of a 20-year-old woman with autoimmune polyglandular syndrome-associated keratopathy who developed acute transplant rejection after keratolimbal allograft (KLAL) surgery. CASE: Nine weeks after KLAL surgery, a 20-year-old woman with autoimmune polyglandular syndrome-related limbal stem cell deficiency presented with graft injection, hemorrhage, and an epithelial rejection line. This was concerning for acute rejection in the setting of triple-agent systemic immunosuppression (albeit nonadherence at times). There was initial reversal of the rejection process with a sub-Tenon's injection of triamcinolone, frequent topical corticosteroids, increase in oral prednisone, and optimization of systemic immunosuppression medications; however, recurrence of the epithelial rejection line and symptoms were noted whenever the prednisone dose was tapered. This was accompanied by ocular surface decompensation (late staining, neovascularization, and persistent epithelial defects). She was found to have weakly positive HLA Class 1 antibodies. The patient was treated with a pulsed corticosteroid infusion and 2 monthly IVIG infusions. This led to resolution of the acute rejection. However, there was a subsequent rejection episode 4 months later after tapering the prednisone. Monthly IVIG for 6 more months led to final resolution with successful prednisone tapering and no further rejection. CONCLUSIONS: Treatment with prolonged IVIG showed better improvement in a case of acute rejection refractory to traditional treatments, especially in the setting of HLA antibodies. The case demonstrates that close follow-up with a corneal specialist and collaboration with a transplant specialist is important to monitor for postoperative KLAL rejection.

Nocardia arthritidis scleritis: A case report.

Purpose: This report describes a case and management of a 69-year-old female with infectious scleritis found to be caused by Nocardia arthritidis species. Observations: Our patient presented with severe constant pain in the left eye (OS) following cataract surgery. She had a pertinent past medical history significant for renal transplantation (on oral tacrolimus, mycophenolate, and prednisone). Slit lamp examination OS (1 month after cataract surgery) demonstrated 3+ injection temporally accompanied by scleral thickening and multiloculated abscesses with purulent drainage from small conjunctival erosions. The abscesses were debrided and sent for gram stain and culture. The patient was treated with repeated subconjunctival injections of antibiotics and an antifungal; topical amphotericin, vancomycin, and amikacin; and oral trimethoprim-sulfamethoxazole (double strength). Two separate gram stains with cultures confirmed the diagnosis and species identification. The patient responded well to repeat subconjunctival injections early on in addition to the prescribed regimen, remaining free of disease at the last follow-up (12 months following presentation). Conclusions and Importance: This unique case demonstrates infectious scleritis caused by an uncommon Nocardia species (N. arthritidis) that was successfully treated with similar strategies used for other reported Nocardia species. As Nocardia scleritis can lead to adverse outcomes if not treated promptly and properly, it should be considered on the differential diagnoses in an immunocompromised patient who presents with acute ocular symptoms after any recent ocular surgery.

Phialophora chinensis fungal keratitis: An initial case report and species identification.

Purpose: To report the initial case of microbial keratitis caused by Phialophora chinensis, a rare cause of fungal keratitis. Observations: A 66-year-old gentleman with a complex right eye (OD) ocular history including herpes simplex virus infectious epithelial keratitis with subsequent neurotrophic keratopathy, and prior combined Candida albicans and parapsilosis fungal keratitis presented with pain OD in the absence of an antecedent trauma. The patient was found to have a filamentous fungal keratitis, which was subsequently cultured and identified as Phialophora chinensis by the laboratory. Despite topical and oral antifungal treatment based on sensitivities determined by the lab, the patient ultimately required intrastromal and subconjunctival antifungal injections, corneal crosslinking, and superficial keratectomy with amniotic membrane to clinically improve. The fungal keratitis recurred twice, with each occurrence rapidly progressing to corneal perforation. Months after the second penetrating keratoplasty, the patient's mental status declined due to multiorgan failure. An occult pulmonary malignancy was discovered during this hospital stay, and the patient was lost to follow-up after entering hospice. Conclusions and Importance: We report a unique case of fungal keratitis caused by Phialophora chinensis and the subsequent management, including both medical and surgical interventions. Despite a multimodal treatment regimen, this case demonstrates the recalcitrant and potentially recurrent nature of fungal keratitis caused by P. chinensis.

Presence of Panel-reactive Antibodies after Penetrating Keratoplasty.

PURPOSE: To evaluate the relationship between penetrating keratoplasty (PK) and postoperative PRA level and number of unacceptable antigens. METHODS: A cross-sectionalstudy was performed on patients with history of PK. Patients with prior solid organ transplantation, pregnancy, or blood transfusion were excluded. These findings were combined with a retrospective review. Patients were grouped by single or multiple PKs. The primary outcome was postoperative PRA level. RESULTS: Incidence of postoperative PRA elevation and mean peak PRA was higher in the multiple PK group (p = .08 and p = .010, respectively). Mean number of unacceptable antigens was elevated in the multiple PK group (p = .024). There was a moderately positive correlation between number of PK grafts and PRA level (r = 0.629, p = .0002). CONCLUSIONS: PRA level may be influenced by PKs, with higher PRA associated with increased prior PKs. Further studies are necessary to determine the potential prognostic value.Abbreviations: PK: penetrating keratoplasty; PRA: panel reactive antibodies; OSST: ocular surface stem cell transplantation; LSCD: limbal stem cell deficiency.

Deep Anterior Lamellar Keratoplasty: Can All Ruptures Be Fixed?

PURPOSE: The aim of this study was to report our experience in managing different types of Descemet membrane (DM) ruptures during deep anterior lamellar keratoplasty (DALK). METHODS: This study was a retrospective, consecutive, interventional case series of 1573 DALK procedures conducted on 1244 patients, performed between 2002 and 2017. Inclusion criteria consisted of a minimum of 24-month follow-up. DM rupture incidence, location, and surgical approach for repair were recorded. Postoperative measures were investigated only in eyes that experienced DM ruptures and included best spectacle-corrected visual acuity, endothelial cell loss, double anterior chamber, pupillary block, need for rebubbling, graft clarity, and rejection episodes. RESULTS: One thousand four hundred forty-three eyes met the inclusion criteria. DM ruptures occurred in 119 eyes (8.25%). Seventy-eight percent of DM ruptures were microruptures (≤2 mm), and they occurred more frequently during manual DALK cases. Macroruptures were less frequent (22%), and they occurred more frequently during subtotal and total anterior lamellar keratoplasty (STALK-TALK) cases. In general, DM ruptures mainly occurred in the peripheral cornea (95% of cases). One hundred (84%) of the 119 ruptures resolved by the first postoperative day. Nineteen cases (16%) developed double anterior chamber; all resolved by using different strategies. No intraoperative penetrating keratoplasty conversion was recorded. Pupillary block occurred in 7 cases (5.9%), but no Urrets-Zavalia syndrome was observed. The average postoperative endothelial cell loss was 410 ± 39 cells/mm 2 (19%) at 1-year follow-up, and there was no significant difference between cases requiring a rebubbling and cases that did not ( P = 0.896). All grafts but one were clear at the last follow-up. Graft failure from endothelial decompensation occurred in this lone case (0.8%). CONCLUSIONS: It is worth trying to repair all DM ruptures in DALK, and immediate penetrating keratoplasty conversion should be avoided. Understanding the physiomechanical mechanisms in DALK allows to correctly choose a proper rescue strategy to successfully repair DM ruptures.

Comparison of Persistent Epithelial Defect Treatment With Sutureless Cryopreserved and Dehydrated Amniotic Membrane.

PURPOSE: To compare cryopreserved sutureless amniotic membrane (C-SAM) and dehydrated SAM (D-SAM) outpatient treatment outcomes for persistent epithelial defects (PEDs), analyze risk factors for treatment failure, and identify adverse events. DESIGN: Retrospective, interventional comparative clinical study. METHODS: This study was a multicenter retrospective interventional cohort from 2 tertiary corneal referral practices from 2016 to 2020. The inclusion criteria were as follows: (1) PEDs treated (2) outpatient with (3) either C-SAM or D-SAM. PEDs were defined as epithelial defects present for ≥7 days after failing prior conservative therapy. The primary outcome measure was the resolution or improvement of a PED. The secondary outcomes included analysis of treatment failures and identification of adverse events. A total of 220 PEDs from 204 eyes (197 patients) treated with either C-SAM or D-SAM met the inclusion criteria. RESULTS: A total of 100 PEDs (45.5%) resolved after single amniotic membrane administration, 46.5% (59 of 127) in the C-SAM group and 44.1% (41 of 93) in the D-SAM group (P = .727). Forty-nine PEDs neither improved nor resolved without a significant difference between the C-SAM (21.3%) and D-SAM groups (23.7%, P = .673). There was no statistically significant difference for PED resolution, PED improvement, PEDs that did not resolve/improve, or those requiring surgery between the 2 groups for initial SAM. CONCLUSIONS: C-SAM and D-SAM were both effective for treating PEDs with comparable outcomes for resolution, improvement, and need for additional surgical intervention. Specific differences in adverse events may help dictate clinical use. Inflammatory disease was a risk factor for nonresolution of all PEDs.

Use of Cenegermin in the Presence of Bandage Contact Lenses.

PURPOSE: 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). METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.