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  5. FP559 : What Drives Eye Rubbing In Keratoconus? A Molecular Biomarker Study.

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Dr.Ritika Dalal, D14793, Dr. Ashima Bajaj, Dr. Pallak Kusumgar, Dr. Rohit Shetty

ABSTRACT :

INTRODUCTION

Keratoconus is a bilateral corneal ectasia with prevalence ranging from 500 to 2300 per 100,000 in central India1 .Despite intensive clinical and laboratory investigation, the etiology of keratoconus remains unclear.

Initially being thought of as a non-inflammatory disorder, there is increasing evidence linking it to degradative enzymes and proteinases like matrix metalloproteinase 9 or MMP-9, interleukin-1 or  IL-1 in its pathogenesis, however these roles need to be more clearly defined.

The association between atopy ,eye rubbing due to itch response and resultant keratoconus has been reported in a number of descriptive studies . 2-3The prevalance of eye rubbing in keratoconus cases ranges from  66-80 % , 4 pointing towards the magnitude of disease burden contributed by eye rubbing.

Eye rubbing is increasingly being acknowledged as a risk factor for development of keratoconus5-9, which could be a direct consequence of mechanical trauma to the cornea, resulting in the progressive deformation and thinning of the cornea, which are hallmarks of the disease. The effect of the mechanical stress is further accentuated by the release of proteinases in the stroma, explaining the progressive thinning of the cornea, which in turn makes it more vulnerable to the trauma caused by rubbing; thereby leading to a vicious cycle.

However, not all cases of keratoconus linked with eye rubbing are atopic clinically.

Through this paper, we intend to integrate eye rubbing with the results of previous molecularapproaches for understanding the pathophysiology of keratoconus in patients with no clinical evidence of allergy.

MATERIALS AND METHODS

Explain the type of study, study duration,  clearance from Institutional review board

The study subjects were divided into two groups. Group A had 50 eyes (25 subjects)with keratoconus (KC) without allergic eye disease (AED);and group B (controls) had 60 eyes (30 subjects) with no evidence of keratoconus or any other ocular / systemic co-morbidity.

Subjects in group A had history of eye rubbing, whereas group B cases had no history of eye rubbing. Patients with dry eye, previous history of ocular surgery, corneal scarring, diabetics, hormonal imbalance and auto-immune disorders were excluded from the study.These subjects were given an explanation of the study purpose and invited to participate, after being given an assurance that their participation was voluntary and that their responses would be treated confidentially. All cases were enrolled after prior written informed consent and approval of the Institutional Ethics Committee. Pre- operative and post-operative retinoscopy, slit lamp biomicroscopy and topography using Pentacam (Oculus) and Orbscan were done to classify into different grades of severity as per the Amsler-Krumeich grading system (EXPLAIN THE GRADING SYSTEM IN BRIEF). Tears were collected by means of schirmer’s strips (explain procedure ie Schirmer 1 or 2, with or without anaesthesia and the filter paper used )and blood (? Venous, ?site of blood collection, ? amount) was collected in plain vials, both stored at   -80degreeCelsius until evaluation .  Total levels of Immunoglubulin E (IgE) in the serum and tears collected from the subjects were estimated by Enzyme Linked ImmunosorbantAssay (ELISA) and cytometric bead array (CBA) respectively.

RESULTS

TearIgE levels were significantly elevated in Group A keratoconus or KC patients (579.7±274.8 IU/ml) compared to Group B (7.667±14.02 IU/ml) control subjects (p= 0.0073). Furthermore, the tear IL-13 levels were also significantly elevated (p= 0.0362) in KC (65.49±121.1 pg/ml) over controls (5.513±6.526 pg/ml) . Tear IL-4 levels were evaluated as well and were significantly higher (p= 0.0421) in KC (28.70 ± 65.12 pg/ml) as compared to controls (2.540±9.837 pg/ml). Within the KC group, we observed a clear trend of increasing serum IgE levels across grades, with following values : grade I (336.4±542.8 IU/ml), II (626.3±959.6 IU/ml) and III / IV (659.6±1055 IU/ml). A similar trend was also observed across grades in the tear IgE levels with grade I (41.29±68.13 ng/ml) ,grade II(305.5 ±481.1 ng/ml) and grade III/IV ( 439.2±1330ng/ml).

On analysing Serum IgE and tear IgE levels in KC patients , a positive co-relation was found (p=0.0002) , suggesting that systemic factors do influence the local IgE levels on the ocular surface.ANegative co-relation between tear IgE levels and TCT ( thinnest corneal thickness) MENTION DEFINITION OF TCT AND HOW IT WAS MEASURED  in KC patients (p = 0.0039) was seen but not between serum IgE and TCT .Also, no co-relation between serum IgE or Tear IgE with K1, K2, Kmean, Kmax or BAD-D(PLEASE MENTION WHAT IS KMAX, KMEAN AND BAD-D) could be observed.

DISCUSSION

More recent
reports have substantiated by immunological meansthe clinical impression that atopic disease,in any of its presentations, was more common in keratoconus.10-11

The known immunological disturbance associated with atopic disease,namely,raised serum levels of immunoglobulin E,was also shown to exist at a significant level in keratoconus patients.12IgE binds to the high-affinity receptor FcεRI(PROVIDE FULL FORM)on mast cells which line the body surfaces and serve to alert the immune system to local immune deviation. Once activated, they induce inflammatory reactions by secreting chemical mediators such as histamine and interleukin-13 (IL-13) which activate transient receptor potential channels on sensory nerve endings to trigger an itch response,and hence, eye rubbing, leading to KC progression by increasing protease activity.13

However, eye rubbing is not limited to only atopic individuals, and throughthis study we intend to understand why it happens in individuals with no evidence of any systemic or ocular allergy.Generalised ( both systemic and local) type V hypersensitivity response has been observed in group A of our study, favouring role of IgE and other related mediators in such pathologies and our results suggest that serum IgE levels co-relate with tear levels. So we can hypothesise that occult systemic allergic responses do have ocular effects.

CONCLUSION

Keratoconus can be a type V hypersensitivity response with predominant involvement of eye and especially cornea .Different therapeutic targets have been established to treat the structural pathology in ectatic corneal disorder and their related spectrum of diseases but none have addressed the physiological issue which predisposes such changes in cornea. We have identifiedhigher levels of tear IgEin non-allergic KC patients , suggesting its plausible causal role in KC pathogenesis. Hence, serum and tear IgE level estimation can be used as a marker for early identification, prognostic purpose  as well as a measure for therapeutic response.

REFERENCES

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