Lifitegrast for the Treatment of Dry Eye Disease: Results of a Phase III, Randomized, Double-Masked, Placebo-Controlled Trial (OPUS-3).

PURPOSE: Lifitegrast is a lymphocyte function-associated antigen-1 antagonist developed to reduce inflammation in dry eye disease (DED). We report the results of OPUS-3 (NCT02284516), a phase III study evaluating the efficacy and safety of lifitegrast versus placebo in participants with DED. DESIGN: Twelve-week, phase III, randomized, double-masked, multicenter, placebo-controlled study. PARTICIPANTS: Adults aged ≥18 years with Schirmer tear test (without anesthesia) ≥1 and ≤10 mm, corneal fluorescein staining score ≥2.0 (0-4 scale), eye dryness score (EDS) ≥40 (0-100 visual analogue scale [VAS]), and history of artificial tear use within 30 days of study entry. METHODS: After a 14-day placebo run-in, participants were randomized 1:1 to lifitegrast ophthalmic solution 5.0% or placebo twice daily for 84 days. MAIN OUTCOME MEASURES: The primary efficacy end point was change from baseline to day 84 in EDS. Key secondary efficacy end points were change from baseline to days 42 and 14 in EDS. Other secondary efficacy end points included additional VAS items (burning/stinging, itching, foreign body sensation, eye discomfort, photophobia, pain), ocular discomfort score (ODS), and safety/tolerability of lifitegrast versus placebo. RESULTS: In the study, 711 participants were randomized: placebo, 356; lifitegrast, 355 (intention-to-treat [ITT] population). At day 84, lifitegrast-treated participants experienced significantly greater improvement from baseline in EDS versus those receiving placebo (treatment effect [TE], 7.16; 95% confidence interval [CI], 3.04-11.28; P = 0.0007). Mean changes from baseline in EDS also significantly favored lifitegrast on days 42 (TE, 9.32; 95% CI, 5.44-13.20; P < 0.0001) and 14 (TE, 7.85; 95% CI, 4.33-11.37; P < 0.0001). No statistically significant differences were observed in ODS between treatment groups at days 84, 42, or 14. A greater improvement was observed in lifitegrast-treated participants at day 42 in itching (nominal P = 0.0318), foreign body sensation (nominal P = 0.0418), and eye discomfort (P = 0.0048) versus participants receiving placebo. Most treatment-emergent adverse events were mild to moderate in severity; no serious ocular adverse events were reported. CONCLUSIONS: Lifitegrast significantly improved symptoms of eye dryness, as measured by EDS, versus placebo in participants with DED. Improvement in EDS was observed as early as day 14. Lifitegrast appeared well tolerated.

Keratolimbal allograft.

PURPOSE OF REVIEW: Keratolimbal allograft (KLAL) transplants limbal tissue attached to a corneoscleral carrier from a cadaveric donor to deliver a large number of stem cells to the recipient. The present article will provide a review of KLAL focusing on the recent literature. RECENT FINDINGS: Recent findings pertain to tissue selection, immunosuppression and adverse event profiles, and postoperative complications (particularly related to immunologic rejection). SUMMARY: KLAL permits the treatment of limbal stem cell deficiency eyes when there is no available living-related or autograft tissue with minimal risk of irreversible toxicity from modern systemic immunosuppression. The prevention of immunologic graft rejection with the use of systemic immunosuppression after KLAL is critical and may require extending systemic immunosuppression treatment longer than previously thought. With vigilant postoperative management, KLAL can allow successful treatment of the most severely diseased eyes.

Disaster in Cosmetic Surgery: Inadvertent Formalin Injection During Blepharoplasty.

The authors report a case where formalin was accidentally injected into the eyelids of a 71-year-old woman undergoing blepharoplasty, causing full thickness necrosis of both upper eyelids and ocular complications that required multiple reconstructive surgical procedures.

The clinical characterization and surgical correction of blepharoptosis associated with congenital aniridia.

PURPOSE: To document the clinical characteristics and describe our management of patients with blepharoptosis associated with congenital aniridia. METHODS: Consecutive retrospective case series of patients with congenital aniridia seen at a single institution (Cincinnati Eye Institute) from 1963 to 2010. Surgical correction was performed by 2 surgeons (J.A.N. and R.C.K.). RESULTS: Ptosis associated with congenital aniridia is marked with decreased levator function. Significant comorbid ophthalmologic disease was invariably present, particularly aniridia-associated keratopathy. Complications, most often keratopathy, were common, even following conservative correction. CONCLUSIONS: The degree of ptosis is significant, and levator function is typically reduced. Ocular surface viability appears to play a key role in preoperative, intraoperative, and postoperative management. While we are aware that congenital aniridia is rather rare, we believe these recommendations are generalizable to patients with severe ocular surface disease.

Antibiotic resistance in acute postoperative endophthalmitis.

Acute postoperative endophthalmitis (APE) is a serious, although infrequent, complication of eye surgery that can result in significant morbidity and costs. This review addresses APE risk factors, associated bacterial pathogens, antibiotic resistance, and prevention.

Medically reversible limbal stem cell disease: clinical features and management strategies.

PURPOSE: To describe the clinical features and management strategies in patients whose limbal stem cell (LSC) disease reversed with medical therapy. DESIGN: Retrospective case series. PARTICIPANTS: Twenty-two eyes of 15 patients seen at 3 tertiary referral centers between 2007 and 2011 with 3 months or more of follow-up. METHODS: Medical records of patients with medically reversible LSC disease were reviewed. Demographic data, causes, location and duration of disease, and medical inventions were analyzed. MAIN OUTCOME MEASURES: Primary outcomes assessed included resolution of signs of LSC disease and improvement in visual acuity. RESULTS: 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). CONCLUSIONS: 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.

Effect of loteprednol etabonate 0.5% on initiation of dry eye treatment with topical cyclosporine 0.05%.

OBJECTIVE: The purpose of this work was to evaluate the effect of loteprednol etabonate (LE) before the initiation of topical cyclosporine A (tCsA) therapy in patients with mild-to-moderate dry eye disease. Prospective, multicenter randomized double-masked parallel group clinical study (NCT00407043). METHODS: Hundred and eighteen patients with dry eye disease were randomized to receive either LE and tCsA (n=61) or artificial tears (AT) and tCsA (n=57). Hundred and twelve patients completed the study (LE: n=57, AT: n=55) and are included in the data analysis. Patients self-administered either LE or AT for 2 weeks 4 times per day, followed by tCsA twice per day accompanied by either LE twice per day or AT twice per day for an additional 6 weeks of treatment. Primary outcome measures included the Ocular Surface Disease Index (OSDI) questionnaire, the Likert scale using standardized facial expressions, lissamine green staining, fluorescein staining, and the Schirmer test. Additional measures included global self-assessment, and safety outcomes included slitlamp examination, intraocular pressure, and assessment of visual acuity. RESULTS: Loteprednol etabonate pretreatment significantly reduced tCsA stinging (P<0.05). Both groups showed significantly improved OSDI scores at the 14-, 30-, and 60-day visits. Loteprednol etabonate showed significantly more OSDI improvement than AT. Both pretreatment strategies improved global self-assessment scores, Schirmer test, fluorescein staining, lissamine staining, and adjunctive AT use. Loteprednol etabonate showed superior improvement in Schirmer test, fluorescein staining, and lissamine staining. Intraocular pressure did not increase in either group. CONCLUSIONS: Loteprednol etabonate induction therapy 2 weeks before the initiation of long-term tCsA treatment for chronic dry eye disease provides more rapid relief of dry eye signs and symptoms with greater efficacy than tCsA and AT alone.

Corneal transplantation.

Corneal transplantation or keratoplasty has developed rapidly in the past 10 years. Penetrating keratoplasty, a procedure consisting of full-thickness replacement of the cornea, has been the dominant procedure for more than half a century, and successfully caters to most causes of corneal blindness. The adoption by specialist surgeons of newer forms of lamellar transplantation surgery, which selectively replace only diseased layers of the cornea, has been a fundamental change in recent years. Deep anterior lamellar keratoplasty is replacing penetrating keratoplasty for disorders affecting the corneal stromal layers, while eliminating the risk of endothelial rejection. Endothelial keratoplasty, which selectively replaces the corneal endothelium in patients with endothelial disease, has resulted in more rapid and predictable visual outcomes. Other emerging therapies are ocular surface reconstruction and artificial cornea (keratoprosthesis) surgery, which have become more widely available because of rapid advances in these techniques. Collectively, these advances have resulted in improved outcomes, and have expanded the number of cases of corneal blindness, which can now be treated successfully. Femtosecond-laser-assisted surgery, bioengineered corneas, and medical treatment for endothelial disease are also likely to play a part in the future.

Donor age and factors related to endothelial cell loss 10 years after penetrating keratoplasty: Specular Microscopy Ancillary Study.

OBJECTIVE: To examine the effect of donor age and other perioperative factors on long-term endothelial cell loss after penetrating keratoplasty (PKP). DESIGN: Multicenter, prospective, double-masked clinical trial. PARTICIPANTS: We included 176 participants from the Cornea Donor Study cohort who had not experienced graft failure ≥ 10 years after PKP for a moderate risk condition (principally Fuchs' dystrophy or pseudophakic/aphakic corneal edema). METHODS: Corneas from donors 12 to 75 years old were assigned to participants using a randomized approach, without respect to recipient factors. Surgery and postoperative care were performed according to the surgeons' usual routines. Images of the central endothelium were obtained preoperatively and at intervals for 10 years postoperatively. Images were analyzed by a central image analysis reading center to determine endothelial cell density (ECD). MAIN OUTCOME MEASURES: Endothelial cell density at 10 years. RESULTS: Among study participants with a clear graft at 10 years, the 125 who received a cornea from a donor 12 to 65 years old experienced a median cell loss of 76%, resulting in a 10-year median ECD of 628 cells/mm(2) (interquartile range [IQR], 522-850 cells/mm(2)), whereas the 51 who received a cornea from a donor 66 to 75 years old experienced a cell loss of 79%, resulting in a median 10-year ECD of 550 cells/mm(2) (IQR, 483-694 cells/mm(2); P adjusted for baseline ECD = 0.03). In addition to younger donor age, higher ECD values were significantly associated with higher baseline ECD (P<0.001) and larger donor tissue size (P<0.001). Forty-two of the 176 participants (24%) had an ECD of <500 cells/mm(2) at 10 years and only 24 (14%) had an ECD of >1000 cells/mm(2). CONCLUSIONS: Substantial cell loss occurs in eyes with a clear graft 10 years after PKP, with the rate of cell loss being slightly greater with older donor age. Greater preoperative ECD and larger donor tissue size are associated with higher ECD at 10 years.

The effect of donor age on penetrating keratoplasty for endothelial disease: graft survival after 10 years in the Cornea Donor Study.

OBJECTIVE: To determine whether the 10-year success rate of penetrating keratoplasty for corneal endothelial disorders is associated with donor age. DESIGN: Multicenter, prospective, double-masked clinical trial. PARTICIPANTS: A total of 1090 participants undergoing penetrating keratoplasty at 80 sites for Fuchs' dystrophy (62%), pseudophakic/aphakic corneal edema (34%), or another corneal endothelial disorder (4%) and followed for up to 12 years. METHODS: Forty-three eye banks provided corneas from donors aged 12 to 75 years, using a randomized approach to assign donor corneas to study participants without respect to recipient factors. Surgery and postoperative care were performed according to the surgeons' usual routines. MAIN OUTCOME MEASURES: Graft failure defined as a regraft or, in the absence of a regraft, a cloudy cornea that was sufficiently opaque to compromise vision for 3 consecutive months. RESULTS: In the primary analysis, the 10-year success rate was 77% for 707 corneas from donors aged 12 to 65 years compared with 71% for 383 donors aged 66 to 75 years (difference, +6%; 95% confidence interval, -1 to +12; P = 0.11). When analyzed as a continuous variable, higher donor age was associated with lower graft success beyond the first 5 years (P<0.001). Exploring this association further, we observed that the 10-year success rate was relatively constant for donors aged 34 to 71 years (75%). The success rate was higher for 80 donors aged 12 to 33 years (96%) and lower for 130 donors aged 72 to 75 years (62%). The relative decrease in the success rate with donor ages 72 to 75 years was not observed until after year 6. CONCLUSIONS: Although the primary analysis did not show a significant difference in 10-year success rates comparing donor ages 12 to 65 years and 66 to 75 years, there was evidence of a donor age effect at the extremes of the age range. Because we observed a fairly constant 10-year success rate for donors aged 34 to 71 years, which account for approximately 75% of corneas in the United States available for transplant, the Cornea Donor Study results indicate that donor age is not an important factor in most penetrating keratoplasties for endothelial disease.

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.

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.

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.

Improving awareness, identification, and management of meibomian gland dysfunction.

Ocular surface disorder--and dry eye, in particular--is a leading reason for visits to eye care professionals. It has been generally accepted that meibomian gland dysfunction (MGD) is a leading cause of evaporative dry eye, as well as being associated with aqueous-deficient dry eye. Yet, researchers and clinicians have lacked a global consensus on the definition of MGD, its epidemiology, pathophysiology, and management. Various systemic diseases and medications have been associated with the progression of both dry eye and MGD, as have several ocular disorders beyond those directly affecting the surface. It is in the best interest of patients for clinicians to be able to better identify and diagnose MGD, differentiating it from other ocular surface disorders, and to recognize the effects of MGD on the ocular surface, and thus initiate appropriate therapy. This CME activity provides expert insight into the Tear Film and Ocular Surface Society's International Workshop on MGD consensus report, offering practical application of its findings to better manage MGD patient care, particularly for those patients facing or undergoing ocular surgery.

Anterior Scleral and Limbal Inflammatory Necrosis After Adjuvant Miltefosine for Recalcitrant Acanthamoeba Keratitis.

PURPOSE: The purpose of this study was to report a retrospective case series of anterior scleral and limbal inflammatory necrosis after adjuvant miltefosine for recalcitrant Acanthamoeba keratitis (AK). METHODS: A case series and literature review. RESULT: Four eyes of 3 patients with recalcitrant AK developed anterior scleral and limbal inflammatory necrosis with significant scleral-limbal thinning after treatment with miltefosine. The average age was 38 years, and the average duration of infection before miltefosine treatment was 239 days. All cases required urgent surgical intervention to either prevent or mitigate corneal-limbal perforation. CONCLUSIONS: Miltefosine has been observed to result in the resolution of AK when used as an adjunctive therapy. It may also lead to a consecutive inflammatory necrosis of the anterior sclera and limbus. This inflammatory response may be significant enough to cause rapid scleral-limbal thinning with subsequent perforation.

A Comparison of TearCare and Lipiflow Systems in Reducing Dry Eye Disease Symptoms Associated with Meibomian Gland Disease.

Purpose: To compare TearCare and Lipiflow systems in the ability to reduce the symptoms of dry eye disease (DED) associated with meibomian gland dysfunction (MGD). Methods: In this multicenter, masked, randomized-controlled trial, 235 subjects received a single TearCare treatment (n = 115) or a single LipiFlow treatment (n = 120) and were followed for 1-month post-treatment. DED symptoms were assessed using the Ocular Surface Disease Index (OSDI), Symptom Assessment in Dry Eye (SANDE), and Eye Dryness (ED) questionnaires at baseline and at 1 month. Post-hoc subgroup analysis was conducted on subjects with less severe and more severe gland obstruction determined by baseline meibomian gland secretion score (MGSS). Results: TearCare system significantly improved total OSDI, SANDE, and ED scores from baseline (p < 0.0001) at 1-month follow-up. Subjects with more severe disease (MGSS <7) achieved statistically greater reduction with TearCare compared to LipiFlow in total OSDI score (30.4 ± 2.53 and 21.9 ± 2.37, respectively, p ANCOVA = 0.0160), OSDI Section B score for quality of vision (5.1 ± 0.48 and 3.6 ± 0.45, respectively, p ANCOVA= 0.0206), and SANDE frequency score (51.9 ± 3.70 and 41.5 ± 3.45, respectively, p ANCOVA = 0.0455). Conclusion: TearCare provides significant DED symptom relief at 1 month after a single treatment. Outcomes were consistent in OSDI, SANDE, and ED assessments. In subjects with more severe gland dysfunction, TearCare performed significantly better than LipiFlow in improving quality of vision and overall DED symptom frequency determined by OSDI and SANDE. Clinical Trial Registration Number: NCT03857919.

Acute Corneal Epithelial Rejection of LR-CLAL After SARS-CoV-2 Vaccination.

PURPOSE: The purpose of this study was to report a case of acute corneal epithelial rejection of living-related conjunctival limbal allograft (LR-CLAL) after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination. OBSERVATIONS: A 27-year-old woman developed acute epithelial rejection of LR-CLAL 2 weeks after receiving the SARS-CoV-2 vaccine. She received the LR-CLAL transplant 4 years and 7 months previously and had a stable clinical course with no history of rejection. She had an ABO blood group and human leukocyte antigen compatible donor, no systemic comorbidities, and no rejection risk factors. CONCLUSIONS: The novel SARS-CoV-2 vaccine upregulates the immune system to produce an adaptive immune response. The SARS-CoV-2 vaccine may potentially be associated with increased risk of rejection in those with ocular surface transplants.

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.

Phase 2, Randomized, Open-Label Parallel-Group Study of Two Dosing Regimens of Netarsudil for the Treatment of Corneal Edema Due to Fuchs Corneal Dystrophy.

Background: This phase 2 study evaluated the therapeutic potential of netarsudil to reduce corneal edema and to improve vision in patients with Fuchs corneal dystrophy (FCD). Methods: Patients (N = 40) with baseline central corneal thickness (CCT) of ≥600 µm and best-corrected visual acuity (BCVA) of 70-20 letters (20/40-20/400 Snellen equivalent) were randomized 1:1 to receive netarsudil once a day (QD) or twice a day (BID) for 8 weeks. Primary endpoint was mean CCT change from baseline at week 4. Results: Netarsudil QD and BID significantly reduced CCT at week 4 [mean change (standard error of mean), 28.4 (7.99) µm, P = 0.0021; and 20.1 (8.75) µm, P = 0.0335, respectively]. Five (12.5%) patients achieved complete resolution of corneal edema at week 4. BCVA improved by 3.2 (2.76) letters with QD and 1.5 (2.84) letters with BID, and 10 (25%) patients [5 with QD (P = 0.0078) and 5 with BID (P = 0.0096)] gained ≥10 letters at week 4. Improvements in CCT and vision were observed at week 2 and persisted at week 8, without significant differences between the 2 doses at any time point. Netarsudil QD significantly improved visual acuity and glare factor scores on the Visual Function and Corneal Health Status (V-FUCHS) questionnaire at weeks 4 and 8 (mean change, -0.4 to -0.3; P ≤ 0.0200). Netarsudil was well tolerated. Reticular edema developed in one (2.5%) patient with BID, which resolved with treatment discontinuation. Conclusions: Netarsudil QD led to significant reductions in corneal edema as well as improvements in vision and patient-reported symptoms of glare and visual impairment in patients with FCD. Clinical Trial Registration Number: NCT04498169.