Management of the Nonhealing Cornea

Educational Objectives

The goal of this program is to improve management of nonhealing corneas. After hearing and assimilating this program, the clinician will be better able to:

1. Develop strategies for management of nonhealing corneas associated with neurotrophic keratitis and limbal stem-cell deficiency.

Summary

Neurotrophic Keratitis (NK)

Features: decreased corneal sensation is a hallmark feature; herpetic eye disease is the most common etiology; patients primarily report visual disturbances; stage 1 disease is characterized by punctate keratitis without a frank epithelial defect; in stage 2 disease, an oval-shaped epithelial defect is present; stromal melt tends to occur in stage 3 disease

Treatment: focuses on restoration of corneal integrity and prevention of progression; visual sequalae can occur with all 3 stages, and patients usually also have dry eye disease and meibomian gland dysfunction; management starts with lubrication, removal of offending agents, and treatment of concurrent infection; most patients have positive tear film inflammation and need an anti-inflammatory medication; placement of amniotic membrane may supply neurotrophic factors to the cornea; DREAM study (McDonald et al [2018]) found that placement of a cryopreserved amniotic membrane (Prokera) can improve reinnervation of the cornea and provide protection from the external environment; autologous serum drops provide neurotrophic growth factors that can help with milder cases; bandage contact lenses can be placed in the office for acute management of open sores on the eye; scleral lenses may be used for long-term management when the epithelium is healing poorly and long-term protection is needed; REPARO study (Bonini et al [2018]) found that ≤72% of patients with stage 2 or 3 neurotrophic keratitis had complete resolution with no residual staining of the cornea after 8 wk of cenegermin (recombinant human nerve growth factor) eye drops; 80% of those with complete resolution remained healed after 1 yr; eye pain may develop after 2 to 3 wk of treatment; patient education may help with adherence to therapy

Limbal Stem-Cell Deficiency

Characteristics: early stages are characterized by a loss of limbal architecture, poor definition between the scleral limbus and cornea, and pannus or mild neovascularization; as the condition progresses, growth of secondary irregular epithelium (usually conjunctival epithelium) occurs because the barrier function of the limbal anatomy is lost; in the late stages, conjunctivalization of the cornea, nonhealing epithelial defects, severe scarring, and symblepharon may be observed

Etiology: often observed with long-term use of soft contact lenses in patients with high myopia; these patients develop a sudden intolerance to contact lenses and poor vision, and they often have conjunctival injection, redness, and inflammation; patients are often reluctant to discontinue wearing contact lenses; long-term use of eye drops containing preservatives, glaucoma drops, or antiviral drops (eg, trifluridine) can cause early limbal stem-cell deficiency; an alternative diagnosis should be considered if patient does not respond to topical antiviral agents after 2 wk

Treatment: remove offending agents (eg, contact lenses); consider moving up microinvasive glaucoma surgery for patients with glaucoma; a mild steroid can be given if matrix metalloproteinase-9 test is positive (indicating inflammation of the tear film); treatments for NK can be used for these patients; limbal stem cells may be harvested from the fellow eye if the patient has unilateral limbal stem cell deficiency or from a living related individual or cadaver donor tissue if both eyes are affected; systemic immunosuppression should be considered if tissue is obtained from a donor, but topical immunosuppression may be adequate for patients >70 yr of age

Readings

Bonini S, Lambiase A, Rama P, et al. Phase II randomized, double-masked, vehicle-controlled trial of recombinant human nerve growth factor for neurotrophic keratitis. Ophthalmology. 2018;125(9):1332-1343. doi:10.1016/j.ophtha.2018.02.022; Kate A, Basu S. A review of the diagnosis and treatment of limbal stem cell deficiency. Front Med (Lausanne). 2022;9:836009. Published 2022 May 25. doi:10.3389/fmed.2022.836009; McDonald MB, Sheha H, Tighe S, et al. Treatment outcomes in the DRy Eye Amniotic Membrane (DREAM) study. Clin Ophthalmol. 2018;12:677-681. Published 2018 Apr 9. doi:10.2147/OPTH.S162203.

Disclosures

For this program, the following relevant financial relationships were disclosed and mitigated to ensure that no commercial bias has been inserted into this content: Dr. Farid is a consultant for Alcon Pharmaceuticals, Alderya Therapeutics, Allergan, Bausch and Lomb, Bio-Tissue, CorneaGen, Dompe, Johnson & Johnson Vision, Kala Pharmaceuticals, Novartis, Orasis, Sun Ophthalmics, Tarsus, and Zeiss. Members of the planning committee reported nothing relevant to disclose.

Acknowledgements

Dr. Farid was recorded at the 90th Midwinter Conference: Ophthalmology, held January 7, 2023, in Universal City, CA, and presented by the Research Study Club of Los Angeles. For information on future CME activities from this presenter, please visit https://researchstudyclub.org/2023-Program. Audio Digest thanks the speakers and presenters for their cooperation in the production of this program.

CME/CE INFO

Accreditation:

The Audio- Digest Foundation is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.

The Audio- Digest Foundation designates this enduring material for a maximum of 0.50 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Audio Digest Foundation is accredited as a provider of continuing nursing education by the American Nurses Credentialing Center's (ANCC's) Commission on Accreditation. Audio Digest Foundation designates this activity for 0.50 CE contact hours.

Lecture ID:

OP610903

Expiration:

This CME course qualifies for AMA PRA Category 1 Credits™ for 3 years from the date of publication.

Instructions:

To earn CME/CE credit for this course, you must complete all the following components in the order recommended: (1) Review introductory course content, including Educational Objectives and Faculty/Planner Disclosures; (2) Listen to the audio program and review accompanying learning materials; (3) Complete posttest (only after completing Step 2) and earn a passing score of at least 80%. Taking the course Pretest and completing the Evaluation Survey are strongly recommended (but not mandatory) components of completing this CME/CE course.

Estimated time to complete this CME/CE course:

Approximately 2x the length of the recorded lecture to account for time spent studying accompanying learning materials and completing tests.