Management of ocular surface disease: current and future directions

Ocular surface disease (OSD) encompasses a diverse range of disorders that impact the ocular tear film and integrity of the ocular surface including the cornea, conjunctiva, lacrimal glands, tear film and eyelids. As the main functions of the ocular surface are to maintain corneal transparency and hydration and protection of the corneal and conjunctival epithelium, the loss of ocular homeostasis leads to serious clinical manifestations.

The etiology of OSD is multifactorial and includes a complex interplay of genetic, environmental and social factors. Common disorders of OSD include dry eye disease (DED), meibomian gland dysfunction (MGD), blepharitis, limbal stem cell deficiency (i.e., chemical burns, thermal burns, chronic use of eye drops with preservatives), neurotrophic keratopathy, and immunological conditions such as mucous membrane pemphigoid and Sjögren’s syndrome. The impact of OSD on affected patients is considerable, with decreased visual function, work productivity and quality of life.

The current burden of OSD worldwide is high and continues to grow in our aging population with increased life expectancy. Current estimates of DED alone ranged from 5% to 50% of the general population, with increased prevalence in advancing age and women (1). The age-related linear increase in prevalence was correlated with greater clinical signs of dry eye, not just with symptom report or self-report of a clinical diagnosis. Similarly, the rate of MGD and glaucoma, among other ocular conditions, was also found to increase in prevalence with age. Dr. Kim and co-authors review the well-documented correlation of OSD and glaucoma, with topical glaucoma medications frequently causing adverse effects on the ocular surface, both through direct action of the medications themselves as well as through toxicity from their associated preservatives. Moreover, both diseases not only increased linearly with age, but OSD prevalence was also found to correlate with glaucoma severity (2). We can thus anticipate the prevalence of OSD and its associated economic burden and impact on vision, quality of life and psychological and physical impact of pain will become a greater public health issue as our population matures.

The management of OSD, especially in advanced cases, is among the most challenging diseases for ophthalmologists to treat currently. In this Annals of Eye Science special series of “Ocular Surface Reconstruction/Transplantation”, we explore a contemporary and systematic approach to the management of OSD including cutting-edge diagnostic testing, medical and procedure-based treatments and surgical options.

Dr. Farooq and associates provide a systematic overview of medical management of OSD to treat tear insufficiency, reduce inflammation, resolve infection and improve epithelial pathology. Conservative management often includes artificial tears, warm compresses, lid hygiene, topical ocular anti-inflammatory medications (including cyclosporine A, lifitegrast), autologous serum, platelet-rich plasma and growth factor therapy. In immunological conditions, such as ocular cicatricial pemphigoid, systemic immunomodulators are often utilized for disease management, as reviewed by Dr. Castiblanco. In-office procedures may include amniotic membrane (dehydrated or cryopreserved), amniotic membrane extract eye drops, bandage contact lenses and tarsorrhaphy. However, these treatments may have limited efficacy in severe cases.

Surgical treatments are reserved for advanced cases of OSD. This may include eyelid procedures to improve the oculo-palpebral structures from symblepharon formation or forniceal shortening in order to improve lid positioning and the tear film. Amniotic membrane transplantation is frequently used in reconstructive techniques to help promote corneal healing, as presented by Dr. Al-Mohtaseb and colleagues. Other treatments include conjunctival flaps, which Dr. Gibralter and associates, describe how this procedure is effective in globe retention for individuals who failed previous visually rehabilitating procedures. The conjunctival flap allows healing and stability and for select conditions, can be visually rehabilitated later with sight-restoring surgical procedures.

Severe cases of limbal stem cell deficiency may be treated with limbal transplantation from healthy autologous tissue (conjunctival limbal autograft, simple limbal epithelial transplantation) in unilateral cases or allogeneic limbal tissue (healthy living-related donors or cadaver corneas) for bilateral cases, which are summarized in-depth by Dr. Park and Dr. Trief and associates. Dr. Djalilian and co-authors delve further and present emerging cell-based therapies that are alternative treatments to minimize immunosuppressive regimens after allogeneic transplants. Cultivated limbal epithelial transplantation (CLET) is currently the only approved cell-based therapy for use in the European Union. Cultivated oral mucosal epithelial transplantation (COMET) is a promising treatment, especially as a surface stabilizing procedure, and mesenchymal stem cells have shown encouraging results for restoring the limbal niche.

In cases of corneal blindness, corneal transplantation, from penetrating keratoplasty to lamellar techniques, can be considered. These may often be in combination or follow limbal stem cell transplantation. However, in end-stage cases or in patients with high-risk features predictive of transplant failure, prosthetic corneas (Boston keratoprosthesis) may be employed. Dr. Cortina and associates give a comprehensive update on Boston keratoprosthesis, which as a synthetic implant does not require an optimized corneal epithelium or functional corneal endothelium in order to maintain optic clarity for vision.

Last, Dr. Barmettler and co-authors evaluated the use of corneal neurotization, a novel surgical technique used to restore corneal sensation in patients with neurotrophic keratopathy by transferring a healthy donor nerve to the affected eye around the limbus. It is a promising treatment to address the underlying pathophysiological mechanism of neurotrophic keratopathy by restoring corneal innervation, which provides both sensory and trophic functions of the corneal epithelium.

In conclusion, the treatment of OSD often requires a combination of medical and surgical approaches targeted to each individual patient’s presentation in order to achieve optimal outcomes.

We hope that the articles in this special series by invited worldwide experts will aid in a comprehensive understanding of the current management options of OSD and stimulate further thought and discussion of the recent advances and future exploration of ocular surface treatments.

Acknowledgments

Funding: None.

Footnote

Provenance and Peer Review: This article was commissioned by the editorial office, Annals of Eye Science for the series “Ocular Surface Reconstruction/Transplantation”. The article did not undergo external peer review.

Conflicts of Interest: Both authors have completed the ICMJE uniform disclosure form (available at https://aes.amegroups.com/article/view/10.21037/aes-24-36/coif). The series “Ocular Surface Reconstruction/Transplantation” was commissioned by the editorial office without any funding or sponsorship. Both authors served as unpaid Guest Editors of the series. R.S.C. serves as an unpaid editorial board member of Annals of Eye Science from April 2020 to December 2025. The authors have no other conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

References

1. Stapleton F, Alves M, Bunya VY, et al. TFOS DEWS II Epidemiology Report. Ocul Surf 2017;15:334-65. [Crossref] [PubMed]
2. Skalicky SE, Goldberg I, McCluskey P. Ocular surface disease and quality of life in patients with glaucoma. Am J Ophthalmol 2012;153:1-9.e2. [Crossref] [PubMed]

Joann J. Kang

Roy S. Chuck