EYELID MARGIN DISEASE (BLEPHARITIS AND MEIBOMIAN GLAND DYSFUNCTION): CLINICAL REVIEW OF EVIDENCE-BASED AND EMERGING TREATMENTS.

ABSTRACT: Blepharitis is a common ophthalmic condition with multiple etiologies and no definitive, universal treatment. The treatment modalities for managing lid margin diseases vary depending on the disease's cause, location, and severity. For anterior blepharitis, management options include eyelid hygiene with warm compresses, eyelid scrubs, baby shampoo, and over-the-counter eyelid cleansers. Topical antibiotics and antibiotic-steroid combination drops/ointments for the eye and eyelid may accompany these. For posterior blepharitis/meibomian gland dysfunction (MGD), at-home warm compress or in-office administration of heat therapy/thermal pulsation treatment that aims to clear obstruction in the meibomian glands and restore meibum secretions to maintain a healthy tear film, are recommended. In addition to the above treatment strategies, various other compounds to manage lid margin diseases are in the late stages of development. This review summarizes the available treatment modalities or those in the pipeline for treating blepharitis and MGD.

Risk Factors for Meibomian Gland Disease Assessed by Meibography.

Purpose: To elucidate risk factors for meibomian gland disease (MGD) and understand associated changes in meibography and in relation to ocular surface disease. Patients and Methods: As part of the standard workup for ocular surface disease at a tertiary academic center, 203 patients received an ocular history and lifestyle questionnaire. The questionnaire included detailed inquiries about ocular health and lifestyle, including makeup use, cosmetic eyelid procedures, screen time, and contact lens habits. Subjects also took the standardized patient evaluation of eye dryness (SPEED) II questionnaire. Meibomian gland (MG) dropout and structural changes were evaluated on meibography and scored by three independent graders using meiboscores. Statistical analysis was conducted to identify significant risk factors associated with MG loss. Results: This retrospective, cross-sectional study included 189 patients (378 eyes) with high-quality images for grading, and the average age was 67 years (77% female). Patients older than 45 years had significantly more dropout than younger patients (p < 0.01). Self-reported eye makeup use did not significantly impact MG loss. Patients with a history of blepharoplasty trended toward higher meiboscores, but the difference was not statistically significant. Self-reported screen time did not affect meiboscores. Contact lens use over 20 years was associated with significant MG loss (p < 0.05). SPEED II scores had no relationship to meiboscores (p = 0.75). Conclusion: Older age is a significant risk factor for MG loss. Any contact lens use over 20 years also impacted MG dropout. Highlighting the incongruence of symptoms to signs, SPEED II scores showed no relationship to the structural integrity of MGs.

Geographic Atrophy Management Consensus (GA-MAC): a Delphi panel study on identification, diagnosis and treatment.

BACKGROUND/AIMS: With a paradigm shift in geographic atrophy (GA) treatments now available, establishing consensus on the identification and diagnosis of the disease along with considerations for management of patients with GA will assist eye care professionals (ECP) in their day-to-day practices, leading to improved patient outcomes. METHODS: A modified Delphi panel process (Geographic Atrophy Management Consensus) consisting of three total surveys and one virtual live meeting held between survey 2 and survey 3. Data were collected from July to October 2022. Participants included expert members of the eye care community that have demonstrated outstanding leadership among peers: a steering committee with three ECPs and a 15-member panel divided between five optometrists, five comprehensive ophthalmologists and five retina specialists. Consensus on statements related to the management of patients with GA was calculated using the RAND/UCLA Appropriateness Method. RESULTS: At the conclusion of the third survey, consensus was reached on 91% of the 77 statements. Critical consensus topics include: (1) optical coherence tomography as the favoured method to diagnose and monitor GA, (2) preferred practice patterns regarding referral of patients to retina specialists and (3) treatment criteria given the advent of emerging therapeutics for GA. CONCLUSIONS: Generating awareness of early signs of disease development, progression and identifying the best tools to evaluate GA establishes ideal management and referral strategies. Given the paradigm shift in GA management driven by approved therapies, coupled with the fact that the disease is progressive resulting in devastating vision loss, these strategies are critical to ensure best overall outcomes.

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.

Delphi Panel Consensus Regarding Current Clinical Practice Management Options for Demodex blepharitis.

Purpose: To obtain consensus on Demodex blepharitis (DB) treatment using a modified Delphi panel process. Methods: Literature search identified gaps in knowledge surrounding treatment of DB. Twelve ocular surface disease experts comprised the Demodex Expert Panel on Treatment and Eyelid Health (DEPTH). They completed a live roundtable discussion in addition to 3 surveys consisting of scaled, open-ended, true/false, and multiple-choice questions pertaining to the treatment of DB. Consensus for scaled questions using a 1 to 9 Likert scale was predefined as median scores of 7-9 and 1-3. For other question types, consensus was achieved when 8 of 12 panelists agreed. Results: The experts agreed that an effective therapeutic agent for treatment of DB would likely decrease the necessity of mechanical intervention, such as lid scrubs or blepharoexfoliation (Median = 8.5; Range 2-9). When treating DB, panelists believed that collarettes serve as a surrogate for mites, and that eliminating or reducing collarettes should be the main clinical goal of treatment (Median = 8; Range 7-9). The panelists would treat patients with at least 10 collarettes, regardless of other signs or symptoms and agreed that DB can be cured, but there is always the possibility for a reinfestation (n = 12). There was also consensus that collarettes, and therefore mites, are the primary treatment target and the way by which clinicians can monitor patient response to therapy (Median = 8; Range 7-9). Conclusion: Expert panelists achieved consensus on key facets of DB treatment. Specifically, there was consensus that collarettes are pathognomonic for DB, that DB patients with >10 collarettes should be treated even in the absence of symptoms, and that treatment efficacy can be tracked by collarette resolution. By increasing awareness about DB, understanding the goals of and monitoring treatment efficacy, patients will receive better care and, ultimately, better clinical outcomes.

Clinical diagnosis and management of Demodex blepharitis: the Demodex Expert Panel on Treatment and Eyelid Health (DEPTH).

BACKGROUND: Twelve ocular surface disease experts convened to achieve consensus about Demodex blepharitis (DB) using a modified Delphi panel process. METHODS: Online surveys were administered using scaled, open-ended, true/false, and multiple-choice questions. Consensus for questions using a 1 to 9 Likert scale was predefined as median scores of 7-9 and 1-3. For other question types, consensus was achieved when 8 of 12 panellists agreed. Questions were randomized, and results of each survey informed the following survey. RESULTS: Twelve practitioners comprised the Demodex Expert Panel on Treatment and Eyelid Health (DEPTH). Following 3 surveys, experts agreed that DB is chronic (n = 11) and recurrent (n = 12) and is often misdiagnosed. Consensus was achieved regarding inflammation driving symptoms (median = 7; range 7-9), collarettes as the most common sign (n = 10) and pathognomonic for DB (median = 9; range 8-9), and itching as the most common symptom (n = 12). Panellists agreed that DB may be diagnosed based on collarettes, mites, and/or patient symptoms (n = 10) and felt that patients unresponsive to typical therapies should be evaluated for DB (n = 12). Consensus about the most effective currently available OTC treatment was not reached. CONCLUSIONS: The Delphi methodology proved effective in establishing consensus about DB, including signs, symptoms, and diagnosis. Consensus was not reached about the best treatment or how to grade severity. With increased awareness, eyecare practitioners can offer DB patients better clinical outcomes. A follow-up Delphi panel is planned to obtain further consensus surrounding DB treatment.

Update on Femtosecond Laser-Enabled Keratoplasty.

ABSTRACT: The application of femtosecond lasers to corneal transplantation is an intriguing proposition with many potential benefits to patients with various corneal diseases. The customized trephination pattern for donor and host matching offers many advantages regarding wound integrity and high precision of donor and recipient match at the interface, which should lead to faster healing and visual rehabilitation. Femtosecond laser-enabled keratoplasty (FLEK) is an advancement of conventional trephination penetrating keratoplasty, and in large clinical cohorts to date, there are meaningful improvements in visual outcomes and a lower risk of graft rejection. Femtosecond laser-enabled deep anterior lamellar keratoplasty (Femto-DALK) combines the advantage of a customized trephination pattern with the deep anterior lamellar keratoplasty procedure, which eliminates the risk of endothelial rejection. Furthermore, the precision of the femtosecond laser may offer additional novel approaches to lamellar keratoplasties. In time, advancements in femtosecond laser platforms will help cornea surgeons realize the added benefits and better optimize outcomes for patients, such that the cost-benefit calculus shifts toward wider accessibility for patients. Prospective randomized-controlled trials are needed to definitively determine the impact of femtosecond laser-enabled keratoplasties on long-term outcomes.

The evidence of implanting a different intraocular lens in each eye.

PURPOSE OF REVIEW: To evaluate the growing body of evidence investigating implanting a different intraocular lens (IOL) in each eye. RECENT FINDINGS: Many surgeons have turned to the mix-and-match approach of implanting two different types of IOLs with the goal of achieving an improved range of distances. A number of studies have compared different types of mix-and-match IOL approaches, with promising results that seem to show maintenance of excellent vision at all distances, and high levels of spectacle independence. SUMMARY: The mix-and-match IOL approach appears to be a promising option for patients, maintaining good vision at all distances, especially near and intermediate, which is highly desired by patients. Few studies also showed intriguing secondary endpoints such as decreased unwanted visual phenomena using this method.

Femtosecond laser deep lamellar keratoplasty.

We aimed to develop a novel and effective technique for creating a smooth deep lamellar dissection of the cornea using a femtosecond (FS) laser for deep anterior lamellar keratoplasty (DALK), we conducted a retrospective eye bank study. Thirteen fresh human corneas were mounted on an artificial anterior chamber, and deep lamellar cuts were made with a 500-kHz VisuMax FS laser at a level of 50-80 µm anterior to the Descemet's membrane (DM). A posterior diameter of 8 mm with a side cut angle of 110° was used for the anterior penetrating side cut. The anterior lamellar tissue was bluntly dissected. The residual posterior stromal beds and side cuts were examined with microscopy and intraoperative optical coherence tomography (OCT) and post-cut endothelial cell evaluations. All corneas revealed a smooth residual posterior stromal bed without any visible irregularities or ridges by microscopy and OCT imaging. Six corneas were suitable for post-cut endothelial cell evaluation 2 days after laser cut, with no significant endothelial cell loss post-laser and blunt dissection of the posterior stroma. FS laser deep lamellar keratoplasty utilizing an ultrafast laser to produce a smooth deep stromal dissection followed by blunt dissection and removal of the anterior stromal tissue yields a consistent and smooth residual stromal bed. The creation of a smooth lamellar dissection in the deep posterior cornea may result in more consistent DALK without the need for air bubble or manual baring of DM that has the risk for DM perforation.

Iris Nevus (Cogan-Reese) Syndrome Presenting with Zonular Dehiscence during Cataract Extraction.

The aim of this study was to report a novel presentation of Cogan-Reese syndrome presenting with zonular dehiscence during cataract extraction with intraocular lens placement. A 49-year-old woman presented with worsening vision over 2 years. The examination was significant for bilateral pupil miosis, visually significant cataracts, and unilateral glaucoma. No iris nodules or corneal endothelial disease was observed through slit-lamp examination and specular microscopy bilaterally. Cataract extraction on the left eye was complicated by significant zonular dehiscence. An iris sample taken during the procedure demonstrated histopathologic findings consistent with an iris nodule composed of melanocytic nevoid cells. Cogan-Reese, or iris nevus syndrome, is a subset of iridocorneal endothelial syndrome that usually presents with iridic stromal matting and stromal loss, nodule formation, and secondary unilateral angle-closure glaucoma. Here, we describe a presentation of Cogan-Reese syndrome that presented with pupillary miosis and glaucoma preoperatively, and zonular dehiscence during cataract extraction with no underlying corneal pathology.

The impact of amphotericin B-fortified preservation media on donor rim cultures and posttransplant infection.

Purpose: To determine the impact of amphotericin B supplementation to donor cornea preservation solutions on the rates of positive donor rim fungal cultures and postkeratoplasty fungal infections. Methods: This was a retrospective analysis of cases undergoing corneal transplantations at a single tertiary referral center from 2016 to 2021. Patients undergoing corneal transplantations with and without amphotericin B supplementation to the storage media were reviewed for donor rim culture results and postoperative infection. The primary outcome measures were positive donor rim fungal culture results and postkeratoplasty fungal infection. Results: A total of 1238 corneal transplants were analyzed. Of these, 849 were stored in preservation solution without amphotericin B, while 389 had amphotericin B included. There was a lower incidence of positive donor rim fungal cultures in cases with amphotericin B supplementation (1.8%) compared to the cases without amphotericin B (2.9%), although this difference was not statistically significant (P = 0.24). Of the 389 cases with amphotericin B supplementation, one (0.25%) went on to develop clinically significant infection, while three of 849 (0.35%) cases without amphotericin B developed infection. The sample size was too small to determine the effect of amphotericin B on the incidence of postkeratoplasty fungal infection. Conclusion: The addition of amphotericin B to donor cornea preservation solution resulted in a downward trend of positive donor rim fungal cultures and postkeratoplasty fungal infections, although these differences did not reach statistical significance. Further studies with larger sample sizes are necessary to appropriately determine the impact of amphotericin B supplementation in the storage solution on positive donor rims and postkeratoplasty fungal infections.

The Efficacy of Clinical Tests to Diagnose Evaporative Dry Eye Disease Related to Meibomian Gland Dysfunction.

OBJECTIVES: To determine the efficacy of widely available subtype clinical tests to characterize evaporative dry eye disease (EDED) related to meibomian gland dysfunction (MGD) compared to normal and to validate those clinical cut points in an independent sample. METHODS: A diagnostic accuracy study (52 subjects), an investigator-masked study, was followed by a larger independent sample (364 subjects) analysis to confirm efficacy in normal and EDED subjects. All subjects were 18 years of age and older and were classified using a battery of clinical tests for dry eye that included symptoms, tear meniscus height, tear stability, ocular staining, evaporative-specific tests, and the Schirmer I test. RESULTS: Normal (nondry eye; n = 26) and EDED (n = 26) subjects completed the efficacy study. The global tests of tear breakup time, staining, and symptoms all produced AUCs ≥ 0.70, representing acceptable discrimination. EDED-specific tests of eyelid marginal signs, gland secretion quality, and gland loss did not demonstrate acceptable test efficacy or differences between normal and EDED subjects. In a larger, independent sample of normal and EDED subjects, gland secretion quality and eyelid marginal score achieved acceptable diagnostic levels: AUCs of 0.789 (CI: 0.734-0.844) and 0.729 (CI: 0.648-0.810), respectively, but not lipid interferometry grade or lower eyelid gland dropout estimated using meiboscopy. CONCLUSIONS: Meibomian gland secretion quality is an efficient and useful functional indicator in EDED and should be incorporated into core outcome sets for this dry eye subtype.

Expert consensus on the identification, diagnosis, and treatment of neurotrophic keratopathy.

BACKGROUND: Neurotrophic keratopathy (NK) is a relatively uncommon, underdiagnosed degenerative corneal disease that is caused by damage to the ophthalmic branch of the trigeminal nerve by conditions such as herpes simplex or zoster keratitis, intracranial space-occupying lesions, diabetes, or neurosurgical procedures. Over time, epithelial breakdown, corneal ulceration, corneal melting (thinning), perforation, and loss of vision may occur. The best opportunity to reverse ocular surface damage is in the earliest stage of NK. However, patients typically experience few symptoms and diagnosis is often delayed. Increased awareness of the causes of NK, consensus on when and how to screen for NK, and recommendations for how to treat NK are needed. METHODS: An 11-member expert panel used a validated methodology (a RAND/UCLA modified Delphi panel) to develop consensus on when to screen for and how best to diagnose and treat NK. Clinicians reviewed literature on the diagnosis and management of NK then rated a detailed set of 735 scenarios. In 646 scenarios, panelists rated whether a test of corneal sensitivity was warranted; in 20 scenarios, they considered the adequacy of specific tests and examinations to diagnose and stage NK; and in 69 scenarios, they rated the appropriateness of treatments for NK. Panelist ratings were used to develop clinical recommendations. RESULTS: There was agreement on 94% of scenarios. Based on this consensus, we present distinct circumstances when we strongly recommend or may consider a test for corneal sensitivity. We also present recommendations on the diagnostic tests to be performed in patients in whom NK is suspected and treatment options for NK. CONCLUSIONS: These expert recommendations should be validated with clinical data. The recommendations represent the consensus of experts, are informed by published literature and experience, and may improve outcomes by helping improve diagnosis and treatment of patients with NK.

The corneal endothelium: clinical review of endothelial cell health and function.

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.

Dupilumab Induced Limbal Stem Cell Deficiency.

Dupilumab is a monoclonal antibody that is used for the treatment of atopic dermatitis (AD) in adults. However, increasing reports of ocular complications including conjunctivitis and dry eye disease have been documented. In this report, we describe a case of a patient who developed limbal stem cell deficiency (LSCD) after prolonged Dupilumab use. A 56-year-old Caucasian male with a history of AD presented with gradual onset cloudy vision and extensive diffuse symblepharon resulting from Dupilumab treatment. He was diagnosed with cicatrizing blepharoconjunctivitis and secondary LSCD after slit lamp examination. In conclusion, LSCD secondary to cicatricial disease is a severe adverse ocular complication caused from long-term Dupilumab treatment.

Combined Epithelial, Stromal, and Anterior Chamber Ingrowth After Penetrating Keratoplasty.

PURPOSE: To present a case of primary graft failure after penetrating keratoplasty found to have epithelial ingrowth into the host stroma on histopathologic analysis. METHODS: This is a single observational case report. RESULTS: We herein describe the clinical course of a case of primary graft failure after penetrating keratoplasty. The corneal button was sent for histopathologic analysis. Analysis of the patient's failed corneal button revealed circumferential epithelial full-thickness wound invasion and stromal epithelial invasion into corneal stroma. CONCLUSIONS: Based on histopathologic analysis and this patient's presentation, the stromal ingrowth followed recipient epithelial invasion of the wound and stromal invasion through clefts in the donor corneal edges. Cases of primary graft failure should be assessed for histopathologic evidence of epithelial stromal ingrowth, despite its rarity. To our knowledge, epithelial ingrowth into the corneal donor stroma after penetrating keratoplasty has not been previously reported.

Posterior lamellar keratoplasty: techniques, outcomes, and recent advances.

Over the past 2 decades, posterior lamellar keratoplasty (PLK) has emerged as an alternative to penetrating keratoplasty in the treatment of corneal endothelial disorders. The reasons for this trend include the search for a safer procedure to replace diseased endothelium that provides faster and better visual rehabilitation and reduces the need for postoperative care. Different surgical techniques, surgical instruments, devices, and lasers have been introduced to overcome technical difficulties, thus improving clinical outcomes. Yet, surgeons and eye banks must address the complications and limitations that arise during the transition to these new techniques. This review discusses the most significant aspects of the evolution of PLK, including a detailed description of current techniques and the direction of future treatment for corneal endothelial disease with the use of laser-assisted surgery, bioengineered corneas, cell therapy, and new pharmacologic therapy.

Quantifying Color Vision Changes Associated With Cataracts Using Cone Contrast Thresholds.

Purpose: To evaluate effects of age and simulated and real cataractous changes on color vision as measured by the high-definition cone contrast test (CCT). Methods: Twenty-four healthy volunteers from two cohort studies performed CCT using best-corrected visual acuity, filters, mydriasis, and pinhole correction. Retrospective cross-sectional study of patients seen in eye clinics evaluated the relationship between age and color vision, and age and lens status in 355 eyes. Last, 25 subjects underwent CCT before and after cataract surgery. Results: CCT scores were most reliable in the nonmydriatic condition without pinhole correction. Progressively dense brown filters produced small decreases in S-cone sensitivity. Linear regression analysis of phakic subjects showed a decline for all cone classes with age. Rate of decline was greater for S-cones (slope = -1.09; 95% confidence interval [CI], -1.30 to 0.86) than M-cones (slope = -0.80; 95% CI, -1.03 to -0.58) and L-cones (slope = -0.66; 95% CI, -0.88 to -0.44). CCT scores increased for S-cones but reduced for L- and M-cones in pseudophakic subjects compared with phakic patients. CCT scores after cataract surgery increased for S-cones, M-cones, and L-cones by 33.0 (95% CI, 8.6 to 57.4), 24.9 (95% CI, 3.8 to 46.0), and 22.0 (95% CI, -3.2 to 47.3), respectively. Conclusions: CCT assessment allows for clinically practical quantitation of color and contrast vision improvement after cataract surgery and aging patients who note poor vision despite good visual acuity. Translational Relevance: CCT testing, which quantifies hereditary and acquired color deficiency, can also quantify the degree of cataract severity and, combined with other parameters, can provide more precise guidance for cataract extraction to optimize patient care.