Efficacy of 1% atropine eye drops in progressive myopia in Indian eyes Dr Mihir Kothari Mahatme Eye Hospital and Jyotirmay Eye Clinic [email protected]

Financial Conflicts - None

Introduction Incidence (≥ -1.0 D) • <5% in children < 8 years - WESTERN • 9% to 15% preschool children – ASIAN • 29% of primary school children in Singapore • 6% at 6-year, 70% by 15 years – Taiwan • 85% to 90% of young adults in Singapore and Taiwan • 25% and 50% in the United States and Europe • Higher prevalence in women

Ocular Morbidity with Myopia  Retinal detachment  Lattice, holes, wwop, PVD, Lacquer Cracks and SRNVM

 Macular Choroidal degeneration

 Premature cataract  Glaucoma  Amblyopia (Isoametropic / Anisometropic)  Nystagmus, Esotropia

Retinal Detachment with Myopia • 0.015% < -4.74D • 0.07% 5-6D (5X) • 3.2% WITH ≥-6D (200X) • INCREASED RISK AFTER o CATARACT SX OR = 0.92/D o Nd-YAG CAPSULOTOMY = OR 3.8/D

Macular CNVM Myopia  2X for -1 D to -2 D  4x for -3 D to -4 D

 9x for −5 D to -6 D

ATROPINE AND PIRENZIPINE EYE DROPS • Atropa belladonna • Mechanism of action: 1. Block accommodation Retard axial elongation 2. Non-selective muscarinic antagonist • Reduced dopamine release retinal signals that control the growth of the eye

3. Atropine reach levels in the bloodstream • Suppresses growth hormone secretion from the pituitary gland which could disturb normal eye growth

Inhibition of DNA synthesis and GAG in Sclera M1 and M4 receptors / Amacrine cells

ATROPINE • The first reports of atropine treatment for myopia were by Wells in the 19th century • In 1979, Bedrossian o 1% atropine ointment once at night in one eye for 1 year o Fellow eye as the control o After 1 year, cross over switched to the fellow eye, and the control

eyes showed significant increases in the rate of myopia

Atropine Treatment of Myopia ATOM1 - 2004 • Randomized, doublemasked, placebocontrolled • 1% Atropine in 6-12 years age • 77% reduction in the mean progression of myopia

ATOM2 - 2015 • • • •

0.5%, 0.1%, 0.01% 2-1-2 = on-off-on Dose-related response 0.01% had the least rebound and no side effects

Our experience

Aim Efficacy of 1% atropine eye drops

in progressive myopia in Indian eyes

Subjects and methods • Prospective interventional myopic cohort • Inclusion criteria o o o o o

Age 5-16 years Vision >6/9 >-0.35D (sph eq)/year 100% compliance to treatment >1 years follow up

• Exclusion criteria o o o o

Pathological myopia Out of age range Slow progressors Limited compliance

• Paired t test for pre and post treatment progression • Pearson’s r for correlation coefficient

Protocol • Pretreatment progression was calculated from the cycloplegic refraction from the past medical record • Progressive addition photogray lenses were prescribed (lower socio economic class excluded – monovision is usually given by us) • 1% Atropine drops – one drop once at night in each eye was started 2 days after getting used to the new spects • 6 monthly follow up • Vision and refraction assessment with a routine use of duochrome test on CP690 Nidek projector chart under atropine cycloplegia non masked pediatric optometrist • Axial length, accommodation and pupil diameter - not measured

Protocol • Atropine continued till 14 years of age and progression was < 0.25D per year • Night dose of Atropine was converted to daily morning if > 0.5D/year progression • Morning atropine was increased to twice a day (7AM, 1PM) atropine drops if >0.5D/year progression was found despite of daily morning dose • Atropine treatment aborted if o Allergic to atropine o No reduction in progression (by atleast 0.25D per year) despite of twice a day application

Our Data • N=30 • M:F = 15:15

• Mean age: 10y (5-16) • Mean spherical equivalent = -6 D (-2.5 to -15) • Mean duration of treatment 23 months (1-3 years)

Our Data • Rate of Progression (similar to past studies): o 0.6/year before atropine (M Vs F no difference p=0.3, t test) o 0.2/year after atropine (M Vs F no difference p=0.6, t test) o Correlation with age and baseline myopia– NO (r=0)

• Gender / Age / Magnitude of myopia – no effect

Our Data o 17 (57%) had to use it in morning o achieve the target progression of < 0.25D/year (correlation to pretreatment progression as in ATOM 2 – may have had higher progression pretreatment – study not enough powered) o 1 had to use it twice a day o 4 had a break ranging for 5 days to 1 month due to unavailability o 1 discontinued due to the atropine allergy

Conclusion o 1% Atropine was effective • Irrespective of gender, magnitude and age of the patient • male/female, high/low, all age o Best if instilled in the morning then step down approach o Keep it available in your clinics due to its difficult availability o 0.01% HSOD (ATOM 2) needs further evaluation

0.5%, 0.25%, 0.1% (-0.04D/Y, -0.45D/Y, -0.47D/Y) J Ocul Pharmacol Ther. 1999 Feb;15(1):85-90. Effects of different concentrations of atropine on controlling myopia in myopic children. Shih YF1, Chen CH, Chou AC, Ho TC, Lin LL, Hung PT.

Limitation • Small group • No comparison with 0.5%, 0.25% (infact not worth it) but 0.01% may be worth it • (Lack of ) Rebound phenomenon is not reported • AXL, Pupil diameter, Accommodation not reported (previous studies many) • Long term safety not evaluated (study was not designed for that, other studies have reported none so far, used since 1979)

Literature • Am J Ophthalmol. 2015 May;159(5):945-9. o There is a small group of children (12.1% younger, with higher myopia, and greater tendency of myopic progression) who may still progress (>0.5D/YR) while receiving atropine treatment

Our study •

3 (10%) patients (one had 0.5D/year and two had 0.9D/year – despite of morning A4) SPH EQ

PROGRESSIO N PRE ATROPINE

PROGRESSION DURATION ADVICE POST MONTHS ATROPINE

8 M

-7

0. 5

0. 5

12 Morning

13 M

-5.5

0.92

0.92

15 Morning

-3

0.92

0.92

24 BD

11 F

Thank you