1. Phospholine Iodide in the management of esotropia Lionel Kowal Claudia Yahalom RVEEH / CERA Melbourne SQUINT CLUB DUNEDIN 2005

2. HISTORY France 120y, US 55y  Javal ‘Manuel theorique et practique du strabisme’: bifocals & miotics for ET 1886  Samuel Abraham: Pilo / eserine for ET  46 cases Amer J Ophth 1949: 16/46 ‘helpful’ AJO 1952,1961; JPO 1964,1966

3. CURRENT STATUS:  Difficult to obtain : application to TGA for each patient  Expensive [$A130 a bottle]

4. PARKS 1958 ABNORMAL ACCOMMODATIVE CONVERGENCE IN SQUINT n=1249  Old / difficult: Why bother?  because it sometimes works very well!

5. PARKS 1958 ABNORMAL ACCOMMODATIVE CONVERGENCE IN SQUINT n=1249  No Rx: n=73  Isoflurophate n=47.. after Rx is stopped  BMR n=10418: no better  One MR n=7426: no better

6. PARKS 1958 number where A:AC improved [ result perfect] No Rx MioticBMR One MR < 7y 9/3129%4/1527% 7 -12y 20/40 28/32 87% All 69 / 104 66%[40;38%] 27 /74 36%[7;9.5%]

7. PARKS 1958 ABNORMAL ACCOMMODATIVE CONVERGENCE IN SQUINT  The lasting improvement of the abnormal A:AC produced by miotic is similar to the permanent result attained by surgery

8. Patients studied  Retrospective chart review of patients from a private strabismus practice.  20 consecutive children with ET reluctant to wear glasses  PI “second choice” for mgmt of ET  Ages 0.5 to 6 y [Parks : low expectations of success - 25+%]

9. Four groups of children with ET A. Hyperopes <+4 who refuse glasses: n=5. A. Hyperopes <+4 who refuse glasses: n=5. B. Hyperopes >+4 who refuse glasses: n=7 B. Hyperopes >+4 who refuse glasses: n=7 C. Uncosmetic near- only ET: n=1 C. Uncosmetic near- only ET: n=1 D. Recurrent ET after initially successful outcome from recent ET surgery. D. Recurrent ET after initially successful outcome from recent ET surgery. Glasses not tolerated / refused n=9 2/9 had an unsuccessful trial of PI prior to surgery

10. Definition of Outcomes  Success (S). Esophoria / tropia ≤10∆ whilst using +/- after stopping PI  Relative success (RS). One of: *decreased angle of ET (either D or N = 0) *% of time strabismic reduced to < 25%  No success (NS): little / no improvement in angle or POTS

11. Table 1: Results of patients receiving PI according to indication for treatment # A: Hyperopia <4 B: Hyperopia > +4 C: Near only ET D: ‘Rescue’ recurrent ET 1 RS 4/12 2 RS: decreased angle 3 S (with later relapse) 4RS 5S 6NS 7NSS 8NS 9S 10NS 11S 12NS 13RS 14 Lost f/u 15 16NSS 17NS 18S 19RS 20 NS (not tolerated)

12. HOW GOOD WAS IT?  A / B / C : 2 successes / 13 pts  D [recurrent ET]: 5-8 success / 9 pts  13 + 9 = 22; 2 pts had PI @ 2 different stages of their course  A/B/C: 2 lost to followup

13. PI RESCUE FOR RECURRENT ET #19 RS  Cong ET. BMR 5.5 /LR Rs OU/ slipped LLR / LLR advanced - all between 7 and 15 mo. CR +2.  Straight.  24 mo: recurrent ET. CR +4.25, +4.5.  Gls refused - PI.  Usually straight.

14. PI RESCUE FOR RECURRENT ET #4 RS  BMR 4.5 @ 14 mo for ET onset 10 mo  Initially perfect  Later ET 0-15ET’ 0-25  PI ET 0ET’ 0-20

15. PI RESCUE FOR RECURRENT ET #17 NS BMR 6.5mm for ET 35-40 / 40-57 BMR 6.5mm for ET 35-40 / 40-57 CR + 1.5  W1 Orthotropia  W8 ET 25 / 30  PI : No effect  M6 : LR Rs OU

16. PI RESCUE FOR RECURRENT ET #13 RS  3yo ET 25/35.  CR +2.25, +1.5 BUT +1 blurs OU.  ET 0-40/ 30-60. BMR 6.5.  W1 Orthotropic D&N.  M3 ET 14 / 18.  M7 ET 20 / 35  PI ET 0 / 25 - 30  + 0.5 DS blurs OU

17. PI RESCUE FOR RECURRENT ET #5 S  8 mo ET 50. CR +2. BMR 6  3w: [ET’]  POTS bad day >50%  6w: PI POTS 0%  Taper over 9 mo stays good

18. PI RESCUE FOR RECURRENT ET #18 S  ET 45/60.  CR +1.25. BMR 6.5  D6 Orthotropic D&N  W4 ET 25-30  PI Orthotropic 4mo f/up

19. PI RESCUE FOR RECURRENT ET #7 NS then S  i/mitt ET from 3mo  +4.5 DS OU  9mo ET<30, ET’ 30  Refused gls. Screamed with PI  15 mo: ET’ 35 BMR 5  D1 slight XT.  M2 ET 20. CR +3.75, +3  Gls refused. PI.  3.5 y: gls. Orthotropic D & N

20. PI RESCUE FOR RECURRENT ET #16 NS then S  2 mo: [ET]. CR +3 DSOU  6 mo: ET 30∆, CR +1.5, +1.  9 -23 mo: I/mitt ET’  23 mo: ET’ 25∆.  32 mo: PI. Deteriorated to ET/ET’ 30-35/30-45∆  BMR 5.5.  D6: XT8∆, small X’D15: ET’6∆.  W5: ET 10/16∆CR/MR +0.75.  PI E/E’ 6∆  8 mo postop: uses PI on bad days

21. PI RESCUE FOR RECURRENT ET #3 S 54 mo: ET 30/ 50 [X2] & 25 / 30. CR +0.5  BMR 5.5. [XT]. D3: Lang 3/3  D 19: ET’ 30. Gls tried / refused. Rx: PI  Next 5 mo: reduced to 2ce weekly.  5mo: orthophoric, BIFR > 12  Stop PI @ 6 mo  10 mo: ET’ 35; EX=0, FR>6.  MR= CR= +0.75 DS OU  Rx: bifocals with +3 add: STRAIGHT

22. Results: success  PI clearly successful in 2 pts [of 7] in group B with >+4. PI treatment continues.  5 pts [of 9] in group D had clear success, allowing these pts to avoid or delay repeat surgery.  2/5 still need daily PI.  1/5 uses PI if ET is seen (‘bad days’)  2/9 patients in “successful” for 2-4 months, and then  to bifocals / SV glasses

23. PROBLEMS WITH MIOTICS  Mims:  279 of his pts + 323 pediatric ophthalmologists surveyed:  Iris cysts 1  Intolerance to hyperopic correction 1  LK:  Screaming after instillation n=1  15+ yrs ago: Iris cysts

24. ISOFLUROPHATE FOR RECURRENT ET Mims & Wood BVQ 1993;8:11-20  n =117  57/117: ET < 8∆, ET’ < 20∆  38/57 [67%]: initial response  16/57 [28%]: no other Rx

25. Summary  PI is a useful adjunct in treatment of recurrent ET.  In patients for whom surgery was followed by an early recurrence of ET with + : PI might help to avoid/delay further surgery even if unsuccessful preop.

26. Aphorism of Hippocrates 300BC Life is short The art long Opportunity fleeting Experiment treacherous Judgement difficult

27. Conclusion PI has a useful role in the treatment of recurrent ET, if glasses will not be worn.

28. Postoperative Miotics for patients with infantile esotropia Spierer A, Zeeli T. Ophthalmic surgery and lasers. Dec 1997(28) 1002-5  Retrospective study including 42 children who underwent BMR recession for cong. ET.  2 groups: the treatment group (20 children) who got PI 1 drop/day for 4/12 1 week after the surgical procedure, and the control group (21 children)  Twelve months postoperatively, the residual/recurrent ET increased an average of 1.4 and 2.8 D in the treatment and control groups respectively (not statistically significant) Amblyopia was more prevalent in the treatment group (20% and 5% respectively) Surgeons decided arbitrarily whom to treat with PI

29. References  Spierer A. Postoperative miotics for patients with infantile esotropia. Ophth surg and lasers. 1997;28:1002-5.  Parks M. Management of acquired esotropia. Brit J Ophthal. 1974;58:240-6.  Hiatt R. Miotics vs glasses in esodeviation. J Ped Ophthal and strabismus. 1979;16:213-7.  Hiatt. Medical management of accommodative esotropia. J Ped Ophthal and strabismus. 1983;199-201.  Goldstein JH. The role of miotics in strabismus.Surv Ophthalmol. 1968;13:31-46.  Abraham SV. The use of miotics in the treatment of nonparalytic convergent strabismus. A progress report. Am J ophthalmol. 1952;35:1191-5.

30. References  Parks M.  ABNORMAL ACCOMMODATIVE CONVERGENCE IN SQUINT  AMA Archives of Ophthalmology  1958: ;364-380

31. Treatment groups Child with Esotropia A- Low Hypermetropia B- High hypermetropia C- Near only ET D- Residual / Recurrent ET s/p Sx

32. Kids with ET and low plus (<4), who didn’t accept glasses: group A Age yrs CR ET type PI tx Results F/U (m) 24 +3.75 ou Cong. 65^ 2/12RS8 70.5 +2.75 ou Cong. Int. 40^ Pre-op Post op →NS→S36 80.5 +1.50 ou R s/p IO – For SO palsy. ET 20^ 3/12NS10 102 R + 1.50 L + 3.00 ET 20^ M/p no amblyopia 2/12NS9 166 +1.00 ou Alt ET 20^→ 2 yrs later 35^ Pre-op Post op →NS→S38 Patient #2: ↓ angle of ET to 50 ^. Then BMR was done. Patients #7 and #16 had a residual ET 15-20^ shortly s/p Sx.

33. B: ET and >+4 # Age yrs CR ET type & size PI tx Results F/U (m) 10.8+4.50 Cong ET 25∆ 4/12RS14 61.4 R+ 6.75 L + 5.25 A. ET 30∆ 2/12NS12 91 +6 OU A. ET 25 ∆ Ongoing for 4/12 S6 114 +5 OU PA/A ET 20∆ Ongoing for 6/12 S6 120.8 +4 OU PA/A ET 30∆ 1/12NS8 154 +4 OU Cong. ET 45∆ 1/12NS Lost f/u 201.5 +4 OU PA/A ET 40∆ Not tolerated NS6 #1:↓ POTS for 4/12. Later ET 60∆→BMR A.ET = accommodative ET. PA = partially accommodative

34. C: near only ET # Age yrs CR ET type PI tx Results F/U (m) 141.9 +1.50 OU Int. ET for near 1/12?6(lost)

35. PI RESCUE FOR RECURRENT ET #19  ‘Large’ cong ET. BMR 5.5 @ 7mo, residual ET, LR Rs OU @ 15 mo. CR +2.  D1: ET 50. slipped LLR.  OR: RLR advanced, RMR 9 from limbus - Botox, LMR 11 from limbus.  Postop: XT, face turn. Straight.  24 mo: recurrent ET. CR +4.25, +4.5.  Gls refused - PI.  Usually straight.

36. PI RESCUE FOR RECURRENT ET #4  10 mo [ET]  13 mo 2514 mo 30  BMR 4.5  ET 0-15ET’ 0-25  PI ET 0ET’ 0-20

37. PI RESCUE FOR RECURRENT ET #13  3yo ET for 6mo. ET 25/35.  CR +2.25, +1.5 BUT +1 blurs OU.  ET 0/30, 25, 40/60. BMR 6.5.  W1 early XT by history. Orthotropic D&N.  M3 ET 14 / 18.  M7 ET 20 / 35  PI ET 0 / 25 - 30  + 0.5 DS blurs OU

38. PI RESCUE FOR RECURRENT ET #5  8 mo ET 50. CR +2. BMR 6  3w: [ET’]  POTS bad day >50%  6w: PI POTS 0%  Taper over 9 mo stays good

39. PI RESCUE FOR RECURRENT ET #17  ET since 12 mo  35-40 / 40-57 CR + 1.5  BMR 6.5  W1 Orthotropia  W8 ET 25 / 30 CR + 1.25  PI : No effect  M6 : LR Rs OU

40. PI RESCUE FOR RECURRENT ET #7  i/mitt ET from 3mo;1st seen 6 mo  +4.5 DS OU EX=0  9mo ET<30, ET’ 30  Refused gls. Screamed with PI  15 mo: ET’ 35 BMR 5  D1 slight XT.  M2 ET 20. CR +3.75, +3  Gls refused. PI. Variable compliance.  3.5 y: gls. Orthotropic D & N

41. PI RESCUE FOR RECURRENT ET #16  2 mo: [ET]. CR +3 DSOU  6 mo: ET 30∆, CR +1.5, +1.  9 -23 mo: varying POTS. [ET’].  23 mo: ET’ 25∆.  32 mo: PI. Good response then deteriorated to ET/ET’ 30-35/30-45∆  BMR 5.5.  D6: XT8∆, small X’D15: ET’6∆.  W5: ET 10/16∆CR/MR +0.75.  PI E/E’ 6∆  8 mo: uses PI on bad days

42. PI RESCUE FOR RECURRENT ET #3 [ET’] onset 4. CR +0.50.  54 mo: ET 30, ET’ 50 [X2]; 25 / 30  BMR 5.5. [XT]. D3: Lang 3/3  D 19: ET’ 30. Gls tried / refused. Rx: PI  Next 5 mo: reduced to 2ce weekly.  5mo: orthophoric, BIFR > 12  Stop PI @ 6 mo  10 mo: ET’ 35; EX=0, FR>6.  MR= CR= +0.75 DS OU  Rx: bifocals with +3 add

43. D: PI “rescue ” for recurrent / residual ET following surgery Age yrs CR ET type & size in ∆ PI tx Results Time off PI F/u months 34Plano N 50 D 30 Res. N ET. Tx for 4/12 S → Later relapse 4/12→Rec N ET→Bif. 18 40.8Plano Cong. ET 20 Rec.ET20∆ Tx for 3/12 SOngoing16 50.8 +2.00 ou Cong.ET50^ Res N ET Tx for 6/12 SOngoing PI on bad days only 12 70.5 +2.75 ou Cong. Int.40 Res.ET20^. Tx for? S15/1236 133 R +2.50 L +1.50 R ET Int.30 Res.ET25^. Tx for ? S → Later relapse 2/12 → Rec N ET→Bif. 20 166 +0,75 ou Alt ET 35 Pre BMR : NS S Ongoing for post op recurrence 38 171.8 +2.00 ou N 50 D 35 Res.ET25^. Tx for 2/12 NS14 185 +1.00 ou ET 45 Res.ET25^. Tx for 1/12 Songoing3 191 +4.50 ou Cong ET s/p 2 sx. 50^ Res.ET25^. Tx for 3/12 RS for 3/12 24

44. Results: (RS) Relative success RS was seen in: RS was seen in:  1 patient in group A (↓strabismic angle)  1 patient in group B (↓POTS)  1 in group C (ortho for 3 months)

45. PI RESCUE FOR RECURRENT ET #18  ET onset 3. 1st seen age 5. ET 45/60.  CR +1.25. BMR 6.5  D6 Orthotropic D&N  W4 ET 25-30  PI Orthotropic 4mo f/up

46. PROBLEMS WITH MIOTICS  1. Cataract - only in the elderly glaucoma population  2. Cholinergic crisis in unrecognised myesthenic n=1  3. Iris cysts  4. Reduced plasma cholinesterase  5. Transient myopia  6. Retinal detachment  7. SLUD salivation / lacrimation / urination/ defecation