Cole Eye Institute, Cleveland Clinic Foundation, Prevalence of Blepharitis Signs and Symptoms Amongst Patients With Age Related Macular Degeneration. Rishi P. Singh, MD Cole Eye Institute, Cleveland Clinic Foundation, Cleveland Ohio Financial Disclosure: The author is a consultant to Oraya Therapeutics, Inspire, Alcon, and Genentech. 1

Purpose It has been recommended that prior to intravitreal injections, the ophthalmologist should identify and treat patients with comorbidities that predispose to endophthalmitis, specifically patients with active blepharitis. However, little is known on the rates of blepharitis within this treatment population. The purpose of this study is to determine the rates of anterior blepharitis amongst patients eligible for intravitreal injection for age related macular degeneration. 2

Methods In this IRB approved study, patients with both dry and wet AMD were assessed for frequency of common ocular surface symptoms associated with blepharitis with a self-reported survey. The patients scored their responses on a scale of 0-4 (0-no symptoms, 1-mild, 2-moderate, 3-severe, 4-very severe). The masked investigator also performed a clinical examination scored both eyes for signs of blepharitis. 3

Methods: Self Reported Patient Questions Eyelid itching: Do your eyelids feel itchy? (0) None: My eyelids do not feel itchy. (1) Mild: Once in a while, my eyelids feel slightly itchy, but I do not have a desire to rub them. (2) Moderate: Occasionally, my eyelids feel itchy, and I need to rub them. (3) Severe: It is difficult to relieve the sensation of itchiness even when I rub my eyelids. (4) Very severe: I have unbearable eyelid itching with an irresistible urge to rub my eyelids. Foreign body sensation/sandiness, grittiness: Do you feel like there’s something sandy or gritty in your eye? (0) None: My eyes do not feel sandy or gritty. (1) Mild: I am aware of the surface of my eyes once in a while. (2) Moderate: My eyes feel like there is something small in them occasionally. (3) Severe: My eyes feel like there is something large or gritty in them. (4) Very severe: I am unable to open my eyes due to feeling of a foreign body in myeyes. 4

Methods: Self Reported Patient Questions Ocular dryness: Are your eyes feeling dry? (0)None: My eyes do not feel dry. (1)Mild: I am aware of dryness to the point where I have to blink to feel better (2)Moderate: I am aware of dryness to the point where I desire to use artificial tears occasionally. (3)Severe: I am aware of dryness to the point where I desire to use artificial tears frequently. (4)Very severe: I am aware of dryness, to the point where I always desire to use artificial tears. Ocular burning or pain: Are your eyes burning or painful? (0)None: My eyes do not burn or ache. (1)Mild: I am aware of the surface of my eyes; they mildly burn or ache. (2)Moderate: I feel my eyes are burning, but still tolerable (3)Severe: My eyes feel throbbing or fiery due to burning/pain. (4)Very severe: I am unable to open my eyes due to burning/pain. 5

Methods: Masked Investigator Scoring Severity Plugging of the meibomian gland (in the middle part of lower lid, n=10) (0) Normal: Clear orifices of meibomian glands in the middle part of lower lid (n=0) (1) Mild: Less than 1/3 of orifices but at least one contain turbid secretions (n=1-3) (2) Moderate: Between 1/3 and 2/3 of orifices contain turbid secretions (n=4-6) (3) Severe: More than 2/3 of orifices but not all contain turbid secretions (n=7-9) (4) Very severe: All orifices plugged with turbid or coagulated secretions (n=10) Secretion expressed from the meibomian gland (0) Normal: Minimal clear, oily secretion (1) Mild: Cloudy secretion (2) Moderate: Granular secretion (3) Severe: Paste-like secretion (4) Obstructed: No expressible secretion 6

Methods: Masked Investigator Scoring Severity Lid debris (collarettes, clumps/strands) (0)Normal: Clear eyelid margin (1)Mild: Occasional fragment, 1-5 collarettes (2)Moderate: Few fragments, 6-20 collarettes (3)Severe: Many fragments, 21-40 collarettes (4)Very severe: Clumps/strands, >40 collarettes Eyelid margin erythema (0) Normal: Normal age-related redness and vasculature. (1) Mild:Slightly dilated blood vessels; vessels colored pink; present in the middle 2/3 section of the lower eyelid margin. (2) Moderate: More apparent dilation of blood vessels; vessel color more intense, whole margin of the eyelid is involved. (3)Severe: Increased vascularity of the eyelid margin, numerous and obvious dilated blood vessels, deep red in color, whole margin of the eyelid is involved. (4)Very severe: Clearly increased confluent vascularity of the eyelid margin; large, numerous dilated blood vessels characterized by deep red color, whole margin of the eyelid is involved. 7

Results: Demographics 50 patients: Sex: 21 male, 29 female Age: 78.1 ± 8.48 years AMD Status: Non-exudative (n = 21) Exudative (n = 29) 32% had a history of dry eye or blepharitis prior to examination 26% had a history of rosacae. 8

Results: Symptoms of Blepharitis by Patient Reported Survey Example: Eyelid Itching Patients reported the following symptoms: Eyelid itching – 1.2 Foreign body sensation – 1.1 Ocular dryness - 1.2 Ocular burning/pain – 1.1 Swollen heavy lids – 0.8. 9

Results: Signs of Blepharitis Masked Physician Recorded Symptoms: Lid debris – 1.5 Eyelid margin erythema – 1.7 Plugging of meibomian glands -1.5 Secretion expressed from the meibomian gland – 1.9. Example: Lid Debris 10

Results: Self-reported patient surveys and masked investigator examinations demonstrated similar-high prevalence of blepharitis (86% and 94% respectively). Fourteen percent of total patients reported no symptoms, and six percent had no clinical signs of blepharitis. Most patients had mild to moderate disease. The incidences were 50% and 36% for mild, 32% and 50% for moderate, and only 4% and 8% for severe symptoms and signs of blepharitis, respectively. Self-reported symptom scores were generally lower than clinical examination scores. The study strengths include that it was a prospective study, masked investigator, and patients were randomly chosen from AMD panel. The study weaknesses include that it was performed at a single site, by a single investigator. Adding photo grading by masked individuals may have improved the scientific method. 11

Conclusions: The prevalence of blepharitis is very high in the AMD patient population who may require frequent intravitreal injections. Prompt evaluation and control of blepharitis and close adherence to intravitreal injection guidelines may be suggested to minimize possible complication with endophthalmitis. 12