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  5. FP690 : Dry Eye Assesment and Importance of Inflammatory Markers in Todays Practice

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Dr. Sujit Addya, A18528, Dr. Dipak Bhuyan,
Dr. Bonomita Neogi

INTRODUCTION

Recent  Definition by TFOS and DEWS II (AUG ‘2017) :

“Dry eye is a multifactorial disease of the ocular surface characterized by a loss of homeostasis of the tear film, and accompanied by ocular symptoms, in which tear film instability and hyperosmolarity, ocular surface inflammation and damage, and neurosensory  abnormalitiesplay  etiological roles

Prevalence : 5 – 34 % depending on the criteria  for DED applied , the population studied , and geographic location 1-5.

According to DEWS II  — 5-50% , higher in Asian population.

. Lee AJ, Lee J, Saw SM, et al. Prevalence and risk factors associated with dry eyes symptoms: a population based study in Indonesia. Br J Ophthalmol 2002;86:1347- 51.

  1. Lin PY , Tsai SY , Cheng CY , et al . Prevalence of dry eye among an elderly chinese population  in Taiwan: the shihpai  Eye  Study. Ophthalmology  2003;110:1096- 101.
  2. McCarty CA, Bansal AK , Livingston PM, et al. The  epidemiology of  dry eye in Melbourne , Australia . Ophthalmology  1998;105:1114- 9.

Risk factors :

General :Ocular :

1) Age : Increases  with age .         1)   MGD .

2) Gender : Women : Men – 2:1.                2)   Blepharitis.

3) Race : Chinese , Hispanics , Asians ,        3)   Conjunctival  disease.

and Pacific Islanders .   4)   Ophthalmic  Surgery .

4) Poor  general health .

5) Medications .

6) Cigarette smoking .

7) Enviromentalconditions .

8) Arthritis.

9) Osteoporosis.

10) Gout.

11) Thyroid disorders. 

MATERIALS AND METHODS

This  is a prospective  study done in 30 patients ,  suspected  of having  dry  eye based on history  and clinical  examination inputs.

CLINICAL EXAMINATION:

All of them underwent  the  following  – Meticulous History , Clinical examination, Ocular  Surface Disease Index (OSDI) score ,Tear film Break up Time (TBUT) , Schirmer’s test OCULAR SURFACE STAINING, Tear Osmolarity level with (Tear Lab)  and MMP- 9 estimation  with  InflammaDry® Package Insert.

Treatment :

  • Patient with tear osmolariry> 315m osm/L and

(a)   Ocular surface staining and MMP9 negative were put on  adequate lubricant.

(b)  Ocular Stain  and MMP 9 positive  were put on lubricants with osmoprotectants,  soft steriod , cyclosporine A , tetracycline and  Omega 3 fatty acids, etc.

RESULTS

Age  and Sex distribution

  • Incidence of dry eye increases with age.
  • It is more significant in the age range above 40 years.
  • Female(56.66%) participants dominated the study.
  • Ocular Surface Disease Index(OSDI) score :
  • Used to categorize the selected patient’s grade of dry eyes.
  • Majority of patients belonged to moderate(63.33%) grade. 

Result of the Tear film 

Break Up Time (TBUT) : 

  • We considered< 10 seconds as Positive / Significant  and  suggestive  of  dry eye.
    INTERPRETATION NUMBER  OF PATIENT (N= 30)
POSITIVE ( TBUT < 10 SEC )         17( 56.66 %).
 TBUT > 10 SEC            8 ( 26.66%).
  INDETERMINATE             5 (16.66%).

Schirmer’sscore :

  • 13(43.33%) patients belong to < 10 mm i.e significant 
  • Low sensitivity and specificity.

STAINING

  • Lissamine green  was  used  for 
  • 4 (13.33%) patient showed stained ocular surface. 

Tear film Osmolarity 

  • Calculated with Tear Lab machine .
  • 315 mOsms/l was taken as the cut off.
  • >315 mosms/l was  tagged as Hyperosmolar tear in our study . 
Tear  film  Osmolarity (mOsms/l)  Number  of  Patients (N  =30)
> 315          17 ( 56.66%)
      315- 310          10 (33.33%)
< 310             3 (10%)

 Detection of Inflammatory markers : MMP9.

  • With InflammaDry® Package Insert .
  • 9 patients exhibited  positive response i.e>40 ng/ml .   
  • Follow Up At 3 Months.

  • OSDI score at  3 months  follow up.

Improvement  is noted

GRADE  OF  DRY  EYE  AS  PER OSDI  INDEX . NUMBER  OF  PATIENTS ( N= 30).
       MILD       16(53.33%)
      MODERATE       12(40.00%)
       SEVERE   2(6.66%)

 Tear lab Osmolarity

At  3 month follow up. 

Tear  film  Osmolarity (mOsms/l) Number  of  patient (N= 30)
> 315    9(30.00%).
    315- 310            15(50.00%).
<310    6(20.00%).

 4 Patient  who exhibited positive staining  were  subjected  to staining at  3 months.

At the end of 3 months of treatment , 1(one)  patient showed  positive

MMP- 9 Level

At  3 months

follow up .

INTERPRETATION  OF  RESULT NUMBER   OF PATIENT POSITIVE AT THE BEGINNING OF THE STUDY (N = 9)
Positive (>  40 ng/ml)     4(44.44%).
Negative (< 40 ng/ml).     5(55.55%).

 DISCUSSION

  • Osmoprotectants( L- carnitine , Erythritol, Betaine and Glycerol ) differentially suppress gene expression , protein production, and enzymatic activity of inflammatory markers in primary HCECs exposed in hyperosmotic  stress1.
  • They may have potential effects in protecting ocular surface epithelia from MMP- mediated disorders in dry eye disease1.

1- Ruzhi Deng, Zhitao Su, Xia Hua, Zongduan Zhang, De- Quan Li, Stephen C. Pflugfelder. – Osmoprotectants  suppress  the production and activity of matrix metalloproteinases  induced  by hyperosmolarity in primary human corneal epithelial cells . Molecular Vision 2014; 20:1243- 1252https://www.molvis.org/molvis/v20/1243.

  • Elevated tear fluid osmolarity has been recognised as a common feature of dry eye for decades1 .
  • Hyperosmotic stress stimulates  the expression and  production of  inflammatory markers including  MMP- 9  by  human corneal epithelial cells(HCEC)2.
  • In our study 4 out of 30 cases showed ocular stain positive , but 9 patient of the same group showed inflamma dry eye test  positive confirming concentration of MMP9 > 40 ng/ml in their tear film.
  • Hence in mild to moderate cases of dry eye patients, ocular surface damage can be identified by Inflama  dry eye test before  ocular surface staining develops.

1- Farris RL. Contact lenses and the dry eye. IntOphthalmolClin 1994;34:129-36 (PMD: 8169066).

       2- Li D- Q, Chen Z, Song XJ, Luo L, Pflugfelder  SC. Stimulation of matrix  metalloproteinases  by  hyperosmolarity  via  a JNK  pathway in  human corneal  epithelial  cells. Invest Ophthalmol Vis Sci  2004; 45:4302- 11(PMD: 15557436).

CONCLUSION

Dry Eye Disease(DED)  is therefore not simply a lack of tears, but a complex surface disease in which the tear film is unbalanced and no longer provides sufficient  nourishment or protection to the ocular surface (reviewed in 2007 Report of the International Dry Eye Workshop (DEWS1).

(1- No authors listed. Report of the International Dry eye Workshop (DEWS) .Ocul Surf 2007;5:1- 204).

Identification  of  inflammatory markers in tear surface  therefore , has  paramount importance in dry eye patients  , so that effective and definitive  intervention can be  taken to  restore cell volume , stabilise  protein function and protect the ocular surface  cells from hyperosmolarity stress .

  • Last but not the least , it can be inferred from  the above discussion  that all these  newer diagnostics and  appropriate intervention  are  likely  to improve the quality of life of the dry eye patients in the  coming years.
  • However longer follow ups  are  required   to throw  more   light on  the

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