Ophthalmology Times Case Study Yasmin Mali, MD Case Study A 57 year old female with presented with ocular irritation and discomfort in both eyes for several months. Patient was previously started on a regimen of artificial tears, lubricating ointment, warm compress, lid scrubs, and omega 3s/fish oil. Despite these treatments symptoms persisted. Past medical history is significant for history of rheumatoid arthritis. Review of systems was otherwise negative. Patient did report current smoking. On ocular examination, patient was found to have decreased TBUT, 4+ diffuse superficial punctate keratopathy both eyes and mild meibomian gland dysfunction. Schirmer s testing revealed less than 5 mm/5 minutes for both eyes. Lissamine stain showed 3+ uptake nasal and temporal conjunctiva. The rest of the slit lamp examination including eyelid position was within normal limits. External examination of the facial skin was normal. Therefore, the decision was made to place right lower and left lower punctual plugs at this visit. Patient returned to the clinic eight weeks later and noted persistent symptoms in both eyes. Corneal staining was significantly improved in both eyes. However, the patient continued to complain of eye irritation and burning both eyes. The patient was found to be positive for matrix metallopeptidase 9 (MMP9) in both eyes. Therefore, the patient was then started on a trial of loteprednol eye drops four times per day in both eyes. Patient returned to the clinic and noted significant symptom relief after only 2 weeks. Therefore, loteprednol drops were reduced to twice a day and cyclosporine A 0.05%drops were initiated in both eyes. At the subsequent follow up visit in 2 months, patient reported that the eye burning and irritation had resolved in both eyes with use of the cyclosporine A 0.05% drops. Discussion Dry eye is a multifactorial disease, which affects the quality of the tear film and ocular surface. Inflammation, tear hyperosmolarity and tear film instability are the main mechanisms by which patients develop symptomatic dry eye. The 2 main categories of dry eye are aqueous tear deficiency (ATD) and evaporative dry eye. Aqueous tear deficiency involves decreased tear production and increased release of inflammatory mediators due to lacrimal gland inflammation. On the other hand, evaporative dry eye is the result of dysfunctioning and obstruction of meibomian glands, which leads to tear evaporation and tear film instability. 1 The patient in our case study has primarily aqueous tear deficiency (ATD) dry eye. Initial treatment for ATD includes topical liquid and gel artificial tears and lubricating ointment. Preservative free formulations are preferred as preservatives increased corneal desquamation. Dietary supplementation with omega 3 fatty acids
are also used in the medical management of dry eye as they block proinflammatory mediators. For moderate dry eye, treatments include punctual plugs and topical anti- inflammatory agents such as corticosteroids or cyclosporine. Additional treatments for patients with severe dry eye include autologous serum tears, scleral contact lenses, permanent punctual occlusion, use of humidifiers and moisture chambers, and tarsorraphy. 2 Inflammation of the ocular surface and lacrimal gland is a key component of the pathogenesis of dry eye disease. Anti- inflammatory agents such as topical corticosteroids and cyclosporine can help to reduce the inflammation. A systemic review and meta- analysis of 12 randomized controlled trials evaluating the effects of topical 0.05% cyclosporine used twice daily showed significant improvement in reflex tear production, corneal fluorescein staining, tear break up time (TBUT), Ocular Surface Disease Index (OSDI) scores and goblet cell density. 3 Topical corticosteroids have been used for pre- treatment prior to initiation of topical cyclosporine drops in patients with chronic dry eye disease. 4 A 2014 study of 112 patients randomized to pretreatment with either topical loteprednol or artificial tears for 2 weeks prior to starting topical cyclosporine drops for mild to moderate dry eye disease. The study found significant improvement in both signs and symptoms of dry eye in the group that received a topical loteprednol prior to initiation of topical cyclosporine. The OSDI scores were significantly more improved compared to the artificial tear group and the Shirmer test, fluorescein staining, lissamine staining showed superior improvement. 5 Conclusion This case demonstrates the multimodal approach to the management and treatment of the inflammatory component of dry eye disease. The use of a combination of anti- inflammatory drops in addition to more conservative treatments can help to reduce patient symptoms and discomfort associated with chronic dry eye. References 1 Weisenthal, RW, et al. "Clinical Approach to Ocular Surface Disorders." Ophthalmology, American Academy of. Basic and Clinical Science Course: External Disease and Cornea. American Academy of Ophthalmology, 2013. 37-57. 2 Bron, AJ, et al. "Rethinking dry eye disease: a perspective on clinical implications." Ocular Surface 12.2 (2014): S1-31. 3 Wan, KH, LJ Chen and AL Young. "Efficacy and Safety of Topical 0.05% Cyclosporine Eye Drops in the Treatment of Dry Eye Syndrome: A Systematic Review and Meta- analysis." The Ocular Surface 13.3 (2015): 213-225. 4 Sheppard, JD, SV Scoper and S Samudre. "Topical Loteprednol Pretreatment Reduces Cyclosporine Stinging in Chronic Dry Eye Disease." Journal of Ocular Pharmacology and Therapeutics 23.1 (2011): 23-27.
5 Sheppard, JD, et al. "Effect of Loteprednol etabonate 0.5% on Initation of Dry Eye Disease Treatment with Topical Cyclosporine 0.05%." Eye Contact Lens 40.5 (2014): 289-296.
Ophthalmology Times Case Study Yasmin Poustchi Mali, MD Department of Ophthalmology Duke University Eye Center July 2016
HPI 57 y.o. F ocular irritation and discomfort in both eyes for several months Persistent symptoms despite using artificial tears, lubricating ointment, warm compress, lid scrubs, and omega 3s/fish oil Review of systems: negative
Past Ocular Hx: DES History Past Medical/Surgical Hx: Rheumatoid arthritis Ocular Meds: AFTs OU QID, lacrilube ointment OU BID Medications: fish oil Allergies: NKDA Social Hx: bank executive, non smoker Family Hx: HTN, DM (parents)
Ocular Exam DVAsc 20/40 20/30 Pupils 4-3 4-3 Ta 14 16 No APD EOM full OU Alignment ortho CVF full OU
Ocular Exam Decreased TBUT 4+ diffuse superficial punctate keratopathy OU Mild meibomian gland dysfunction BUL/BLL Schirmer <5 mm/5 minutes OU 3+ Lissamine uptake nasal and temporal conjunctiva Otherwise slit lamp exam was within normal limits External examination of the facial skin normal Therefore, right lower and left lower punctual plugs were placed
Clinical Course Persistent symptoms in both eyes 8 weeks later at follow up Corneal staining significantly improved OU; however, continued irritation and burning OU noted Patient found to be positive for matrix metallopeptidase 9 (MMP9) OU Started trial of loteprednol drops QID OU
Clinical Course Significant symptom relief OU 2 weeks after starting trial Loteprednol drops decreased to BID Cyclosporine A 0.05% drops BID OU initiated At follow up visit 2 months later, patient symptoms had resolved completely OU with cyclosporine drops
Multifactorial Dry Eye Disease Affects quality of the tear film and ocular surface Primary mechanisms include 1 Inflammation Tear hyperosmolarity Tear film instability
Two Main Categories Aqueous tear deficiency Evaporative dry eye Lacrimal gland inflammation Dysfunctioning and obstruction of meibomian glands Decreased tear production Tear film instability Increased release of inflammatory mediators Tear evaporation
Aqueous tear deficiency 2 Mild dry eye topical liquid and gel artificial tears, lubricating ointment Preservative free formulations Dietary supplementation with omega3s/fish oil Moderate dry eye Punctal plugs Topical anti- inflammatory agents such as corticosteroids or cyclosporine Severe dry eye Autologous serum tears Scleral contact lenses Permanent punctal occlusion Use of humidifiers, moisture chambers Tarsorraphy
Discussion Inflammation of the ocular surface and lacrimal gland is a key component of the pathogenesis of dry eye disease. Anti- inflammatory agents such as topical corticosteroids and cyclosporine can help to reduce the inflammation. A systemic review and meta- analysis of 12 randomized controlled trials evaluating the effects of topical 0.05% cyclosporine used twice daily showed significant improvement in reflex tear production, corneal fluorescein staining, tear break up time (TBUT), Ocular Surface Disease Index (OSDI) scores and goblet cell density. 3
Discussion Topical corticosteroids have been used for pre- treatment prior to initiation of topical cyclosporine drops in patients with chronic dry eye disease. 4 A 2014 study of 112 patients randomized to pretreatment with either topical loteprednol or artificial tears for 2 weeks prior to starting topical cyclosporine drops for mild to moderate dry eye disease. The study found significant improvement in both signs and symptoms of dry eye in the group that received a topical loteprednol prior to initiation of topical cyclosporine. The OSDI scores were significantly more improved compared to the artificial tear group and the Shirmer test, fluorescein staining, lissamine staining showed superior improvement. 5
Conclusion This case demonstrates the multimodal approach to the management and treatment of the inflammatory component of dry eye disease. The use of a combination of anti- inflammatory drops in addition to more conservative treatments can help to reduce patient symptoms and discomfort associated with chronic dry eye.
References 1 Weisenthal, RW, et al. "Clinical Approach to Ocular Surface Disorders." Ophthalmology, American Academy of. Basic and Clinical Science Course: External Disease and Cornea. American Academy of Ophthalmology, 2013. 37-57. 2 Bron, AJ, et al. "Rethinking dry eye disease: a perspective on clinical implications." Ocular Surface12.2 (2014): S1-31. 3 Wan, KH, LJ Chen and AL Young. "Efficacy and Safety of Topical 0.05% Cyclosporine Eye Drops in the Treatment of Dry Eye Syndrome: A Systematic Review and Meta- analysis." The Ocular Surface 13.3 (2015): 213-225. 4 Sheppard, JD, SV Scoper and S Samudre. "Topical Loteprednol Pretreatment Reduces Cyclosporine Stinging in Chronic Dry Eye Disease." Journal of Ocular Pharmacology and Therapeutics 23.1 (2011): 23-27. 5 Sheppard, JD, et al. "Effect of Loteprednol etabonate 0.5% on Initation of Dry Eye Disease Treatment with Topical Cyclosporine 0.05%." Eye Contact Lens 40.5 (2014): 289-296.