Novel point-of-care biomarkers of the dry anophthalmic socket syndrome: tear film osmolarity and matrix metalloproteinase 9 immunoassay

Abstract

Purpose To compare tear film osmolarity (TFO) values and matrix metalloproteinase 9 (MMP-9) levels between anophthalmic sockets and healthy fellow eyes and to assess the use of the MMP-9 and TFO as objective biomarkers for the dry anophthalmic socket syndrome (DASS). Methods In this prospective single-center study, the anophthalmic sockets and healthy fellow eyes of 98 unilateral anophthalmic patients were assessed using the ocular surface disease index (OSDI) questionnaire, InflammaDry® MMP-9 point-of-care immunoassay, TFO with TearLab™ Osmolarity System, and clinical conjunctival inflammation. MMP-9 concentration and conjunctival inflammation were graded semi-quantitatively. Differences between anophthalmic sockets and the healthy fellow eyes for OSDI scores, MMP-9, TFO values, clinical conjunctival inflammation, and eyelid abnormalities as well as the correlation between these factors and demographic data were evaluated. Results Patients had significantly higher OSDI, MMP-9, and TFO values, as well as higher conjunctival inflammation on the anophthalmic side, compared to the healthy side (p ≤ 0.002, respectively). For anophthalmic sockets, there was a significant positive correlation between OSDI scores and TFO values (p = 0.007), between the grade of posterior blepharitis and TFO values (p = 0.026), and between the conjunctival inflammation and MMP-9 values (p < 0.001), as well as between MMP-9 levels and time since eye loss (p = 0.004). Conclusions Measuring MMP-9 and TFO may be helpful tools as efficient, quantifiable biomarkers, disease course parameters, or predictors for treatment response in the clinical management of patients with DASS or future therapy studies. Ophthalmologists should consider the updated diagnosis criteria including TFO and the definition for DASS proposed in this study.

How to analyze conjunctival inflammation in dry anophthalmic socket syndrome (DASS)?

“…Measurements of TFO have been demonstrated to be suitable, and even superior to other forms of tests, in terms of dry eye diagnosis. In anophthalmic eye, TFO values have been measured higher on the anophthalmic side, compared to those on the healthy side [6]. Moreover, a significant positive correlation between OSDI scores and TFO values and between the grade of posterior blepharitis and TFO has been observed, suggesting that TFO seems to play a crucial role in the aetiology of DASS and patient complaints [6].…”

“…In anophthalmic eye, TFO values have been measured higher on the anophthalmic side, compared to those on the healthy side [6]. Moreover, a significant positive correlation between OSDI scores and TFO values and between the grade of posterior blepharitis and TFO has been observed, suggesting that TFO seems to play a crucial role in the aetiology of DASS and patient complaints [6]. Do we need to measure the TFO for all patients with anophthalmic sockets?…”

How to diagnose dry anophthalmic socket syndrome (DASS) in the clinical routine

“…by our highly esteemed colleague and friend Frederic Mouriaux was of great interest to us [ 1 ]. Fortunately, the knowledge regarding DASS is increasing and the pathophysiology of DASS is beginning to be understood [ 2 – 4 ]. Conjunctival inflammation is one of the key factors in DASS, most likely even the cardinal factor and should therefore be targeted for successful treatment [ 1 ].…”

“…When evaluating the subjective symptoms of DASS, standardized questionnaires including OSDI, DEQ-5, or SANDE should be used, separately for the anophthalmic socket and the healthy fellow eye routinely [ 1 – 4 ]. While DEQ-5 and SANDE can be used for healthy eyes and anophthalmic sockets the same way, in OSDI all vision-related questions (i.e., questions according to driving, watching TV) have to be classified as “not answered” for the anophthalmic side [ 2 – 4 ]. The total OSDI scores have then to be calculated based on the following formula (for each side separately): OSDI score = [(sum of scores for all questions answered) × 100] / [(total number of questions answered) × 4] [ 2 – 4 ].…”

“…For a comprehensive evaluation, a standardized clinical basis examination should include slit-lamp examination with special regard to conjunctival inflammation, anterior and posterior blepharitis, eyelid position, blinking rate, and lagophthalmos [ 2 – 4 ]. Measuring the tear film break-up time could also be helpful.…”