The precorneal tear film is the most critical refractive surface in the human optical system. When striving to deliver a glasses-free experience, especially with multifocal IOLs, the preoperative management of dry eye disease (DED) is critical (see The Link Between Dry Eye Severity and Patient Satisfaction). An unoptimized ocular surface during cataract surgery assessments compromises the accuracy of measurements critical to surgical planning.
The Link Between Dry Eye Severity and Patient Satisfaction
A thorough analysis conducted at Center for Sight in 2019 (unpublished data) involving four surgeons and 113 eyes found a direct correlation between dry eye disease severity and patient dissatisfaction following premium IOL surgery. In the analysis, a preoperative complaint of vision fluctuation was closely linked to dry eye disease severity, highlighting the necessity of addressing ocular surface health preoperatively.
Untreated DED can also complicate patients’ postoperative recovery. I therefore advise my patients to prioritize DED treatment before undergoing surgery. This approach not only facilitates a smoother, quicker recovery but also optimizes their chances of achieving the desired surgical outcome.
Comprehensive Preoperative Ocular Surface Assessment
Before I enter the exam room, I review the patient’s testing outside their room. My biometrist will indicate the quality of the measurements on the Notes section of the IOLMaster 700 (Carl Zeiss Meditec) by grading the distortion from 0 to 4+. Specifically, my biometrist looks at the sharpness of the LED light images reflected off the cornea to gauge the degree of distortion. I read her notes before examining the patient and oftentimes already know whether I want to repeat the measurements.
Multiple imaging modalities. Measurements of critical factors such as astigmatism are compared across different imaging systems, such as the IOLMaster and Pentacam (Oculus Optikgeräte). For instance, if a patient is found to have 2.00 D of astigmatism, I look for consistency in this measurement and its axis across both devices. Discrepancies between these readings often point to untreated DED. A detailed, preemptive review process allows me to tailor my approach to address all underlying issues right from the start.
Once I have reviewed a patient’s test results, I personally examine them. My analysis can be divided into two main categories: an evaluation of the eyelids for issues such as meibomian gland dysfunction (MGD) and blepharitis and an examination of the cornea.
Tear film evaluation. Critical insight into the state of the ocular surface is obtained through corneal staining (Figure). At least 2 minutes after the instillation of fluorescein dye, the cornea is evaluated for ocular surface disease (OSD) under cobalt blue light. This process reveals the patterns and distributions of erosions, with findings graded on a scale from 0 to 4 based on the number of punctate epithelial erosions observed. A comprehensive evaluation is crucial for accurately diagnosing OSD severity and tailoring the therapeutic approach. Tear breakup time is also evaluated. Values of less than 10 seconds indicate abnormality, and the presence of vertical streaks may suggest MGD.
Figure. Corneal staining patterns observed during an assessment of the ocular surface with fluorescein dye. A scattered staining pattern indicates the need for a meticulous preoperative evaluation of the ocular surface (A). A diffuse corneal staining pattern is often seen in eyes with various ocular surface disorders (B). The presence of vertical streaking within the tear film is suggestive of MGD (C). Corneal changes characteristic of anterior basement membrane dystrophy/epithelial basement membrane dystrophy (D).
Preoperative Ocular Surface Optimization
My preoperative approach to optimizing the ocular surface is not only diagnostic but also educational. I provide patients with a handout that is updated biannually and outlines all possible dry eye treatments. This handout, which lists everything from heating masks to immunomodulatory drops such as cyclosporine (CsA) ophthalmic emulsion 0.05% (Restasis, Allergan/AbbVie), CsA ophthalmic solution 0.09% (Cequa, Sun Ophthalmics), CsA ophthalmic solution 0.1% (Vevye, Harrow), and lifitegrast ophthalmic solution 5% (Xiidra, Novartis Pharmaceuticals), allows me to mark specific recommendations for each patient. Some over-the-counter products, offered in our office for patient convenience rather than profit, are underlined to suggest that patients can easily purchase them here. For comprehensive OSD management, treatments range from interventions for mild to moderate disease such as preservative-free artificial tears and heat masks to more intensive treatments such as steroids, dissolvable punctal plugs, and device-assisted therapies such as the iLux (Alcon), the LipiFlow Thermal Pulsation System (Johnson & Johnson Vision), and the TearCare system (Sight Sciences).
Regardless of the specific treatment plan, the use of artificial tears is regularly recommended before surgery. Depending on the severity of their OSD, patients may be brought back for follow-up and retesting within 1 to 3 weeks. This comprehensive, patient-centered approach ensures each patient receives individualized care to optimize their ocular health and surgical outcomes. (For an overview of cutting-edge treatments and novel approaches currently in development or recently approved, see Therapeutics Under Investigation in DED Management.)
Therapeutics Under Investigation in DED Management
Novel Mechanisms of Action
AR-15512 (Alcon). This topical transient receptor potential melastatin 8 agonist is a first-in-class product candidate for the treatment of the signs and symptoms of dry eye disease (DED). The primary endpoint was achieved in pivotal efficacy and safety studies (COMET-2 and COMET 3).1
AZR-MD-001 (Azura Ophthalmics). This selenium sulfide ophthalmic ointment met the coprimary endpoints of a phase 2 multicenter study, with a statistically significant improvement in the signs and symptoms of meibomian gland dysfunction. The drug was safe and well tolerated.2 It has the potential to revolutionize the treatment of contact lens–related discomfort by improving meibomian gland function and tear stability.3 Azura is preparing for phase 3 development discussions with the FDA.4
HL-036 (HanAll Biopharma). Tanfanercept targets tumor necrosis factor alpha to mitigate inflammation, a key factor in DED. Its unique formulation allows for oral and ophthalmic administration, offering a potential improvement over existing therapies.5
IVW-1001 (iView Therapeutics). This novel transient receptor potential melastatin 8 agonist addresses the signs and symptoms of DED by targeting cold-sensitive thermoreceptors. The drug promotes tear secretion and alleviates ocular discomfort. FDA approval of the Investigational New Drug application clears the way for the initiation of a phase 1/2 clinical trial.6
Advanced Delivery Systems
OTX-DED (Ocular Therapeutix). This low-dose intracanalicular insert of dexamethasone is designed for the short-term treatment of episodic DED. The preservative-free option could reduce the risk of ocular surface toxicity and is currently undergoing clinical evaluation.7
OTX-CSI (Ocular Therapeutix). This preservative-free cyclosporine intracanalicular insert is designed to deliver therapy for up to 12 weeks with a single application. It is because evaluated for the treatment of DED.8
Under Additional Evaluation
Reproxalap (Aldeyra Therapeutics): Following a Complete Response Letter from the FDA for the New Drug Application for this reactive aldehyde species modulator, additional trials of the investigational drug candidate are underway to demonstrate a positive effect on the ocular symptoms of DED. A New Drug Application resubmission could occur in the first half of this year.9
1. Alcon. Alcon announces positive topline results from phase 3 comet trials of ar-15512, a novel topical drug candidate for dry eye. January 9, 2024. Accessed March 14, 2024. https://www.alcon.com/media-release/alcon-announces-positive-topline-results-phase-3-comet-trials-ar-15512-novel-topical.
2. Watson SL, Jones LW, Stapleton F, et al; CELESTIAL STUDY Group. Efficacy and safety of AZR-MD-001 selenium sulfide ophthalmic ointment in adults with meibomian gland dysfunction: a vehicle-controlled, randomized clinical trial. Ocul Surf. 2023;29:537-546.
3. Azura Ophthalmic announces positive results from phase 2 clinical trial of AZR-MD-001 in patients with contact lens discomfort. Eyewire. December 18, 2023. Accessed March 18, 2024. https://eyewire.news/news/azura-ophthalmics-announces-positive-results-from-phase-2-clinical-trial-of-azr-md-001-in-patients-with-contact-lens-discomfort?c4src=article:infinite-scroll
4. Healio. AZR-MD-001 improves signs, symptoms of meibomian gland dysfunction, topline data show. December 19, 2023. Accessed March 14, 2024. https://www.healio.com/news/optometry/20231219/azrmd001-improves-signs-symptoms-of-meibomian-gland-dysfunction-topline-data-show
5. Tanfanercept by HanAll Biopharma for keratoconjunctivitis sicca (dry eye): likelihood of approval. Pharmaceutical Technology. February 29, 2024. Accessed March 14, 2024. https://www.pharmaceutical-technology.com/data-insights/tanfanercept-hanall-biopharma-keratoconjunctivitis-sicca-dry-eye-likelihood-of-approval/
6. FDA clears iView Therapeutics IND application to start trial of TRPM8 agonist, IVW-1001. Ophthalmology Times. March 12, 2024. Accessed March 14, 2024. https://www.ophthalmologytimes.com/view/fda-clears-iview-therapeutics-ind-application-to-start-trial-of-trpm8-agonist-ivw-1001
7. Sustained-release product candidate to treat episodic dry eye. Ocular Therapeutix. Accessed March 14, 2024. https://www.ocutx.com/pipeline/dry-eye-treatment/
8. Sustained-release product candidate for dry eye disease. Ocular Therapeutix. Accessed March 14, 2024. https://www.ocutx.com/pipeline/dry-eyes-symptoms/
9. Aldeyra Therapeutics receives complete response letter from the U.S. Food and Drug Administration for the reproxalap new drug application for the treatment of dry eye disease. Aldeyra Therapeutics. November 27, 2023. Accessed March 14, 2024. https://ir.aldeyra.com/news-releases/news-release-details/aldeyra-therapeutics-receives-complete-response-letter-us-food
Managing Patient Expectations and Education
Patient education is fundamental to DED management. I emphasize to patients that DED is a chronic condition, not something that will disappear. It requires ongoing management. Individuals receiving certain types of IOLs, such as multifocal lenses, may require lifelong DED management. Patients who grasp the permanence of their condition are more likely to have realistic expectations and adhere to prescribed treatment.
At the time of the consultation, I make it a point to inform every patient about the types of lenses for which they are eligible. When patients present with moderate to severe OSD, the conversation takes a different turn. I tell them up front that their candidacy for multifocal lenses might be limited and the decision hinges on how they respond to treatment. Typically, I schedule a follow-up appointment 2 to 3 weeks later to assess their progress.
In my experience, patients who are informed about their DED at the outset are less likely to be frustrated by postoperative vision fluctuations. Proactive communication fosters a more positive attitude toward their condition and its treatment.
Lens Considerations
Monofocal IOLs. With patients who have severe DED, I often find it necessary to state that, although their condition may improve, I cannot recommend a multifocal lens. I explain that such lenses are particularly susceptible to the effects of DED, which could significantly impair their vision. I advise them that a monofocal lens is their only option.
For patients with moderate disease, the decision is more nuanced and depends greatly on their response to treatment. If, upon reevaluation, the ocular surface shows considerable improvement, and the testing is satisfactory, they may be candidates for a multifocal IOL.
Multifocal IOLs. I emphasize the importance of ongoing ocular surface maintenance to candidates for multifocal lenses. They must be willing to commit to preserving the health of their ocular surface postoperatively. If they are hesitant or unable to make this commitment, I recommend a monofocal IOL as a safer, more suitable choice. This approach ensures that patients are fully informed of their options and the responsibilities associated with each lens and guides them toward the best decision for their vision and lifestyle.
Collaborative Care for Optimal Outcomes
In our high-volume surgical practice, I rely heavily on the expertise of optometrists for the pre- and postoperative care of our patients. Engaging in ongoing education with our comanaging doctors is essential for maintaining the high level of care our patients expect and deserve. For instance, introducing new medications into our treatment protocol requires educating our team about the agents’ benefits and applications.
1. Sheppard JD Jr, Singh R, McClellan AJ, et al. Long-term supplementation with n-6 and n-3 PUFAs improves moderate-to-severe keratoconjunctivitis sicca: a randomized double-blind clinical trial. Cornea. 2013;32(10):1297-1304.
2. Kapoor R, Huang YS. Gamma linolenic acid: an antiinflammatory omega-6 fatty acid. Curr Pharm Biotechnol. 2006;7(6):531-534.
3. Barabino S, Rolando M, Camicione P, et al. Systemic linoleic and gamma-linolenic acid therapy in dry eye syndrome with an inflammatory component. Cornea. 2003;22(2):97-101.
4. Macrì A, Giuffrida S, Amico V, Iester M, Traverso CE. Effect of linoleic acid and gamma-linolenic acid on tear production, tear clearance and on the ocular surface after photorefractive keratectomy. Graefes Arch Clin Exp Ophthalmol. 2003;241(7):561-566.
5. Aragona P, Bucolo C, Spinella R, Giuffrida S, Ferreri G. Systemic omega-6 essential fatty acid treatment and PGE1 tear content in Sjögren’s syndrome patients. Invest Ophthalmol Vis Sci. 2005;46(12):4474-4479.
6. Kokke KH, Morris JA, Lawrenson JG. Oral omega-6 essential fatty acid treatment in contact lens associated dry eye. Cont Lens Anterior Eye. 2008;31(3):141-146.
7. Pinna A, Piccinini P, Carta F. Effect of oral linoleic and gamma-linolenic acid on meibomian gland dysfunction. Cornea. 2007;26(3):260-264.
8. Brignole-Baudouin F, Baudouin C, Aragona P, et al. A multicentre, double-masked, randomized, controlled trial assessing the effect of oral supplementation of omega-3 and omega-6 fatty acids on a conjunctival inflammatory marker in dry eye patients. Acta Ophthalmol. 2011;89(7):e591-597.
