OCULAR LEPROSY

The LOSOL study

What we know now and what we don’t know

What we would like to know – The Research questions

Ebenezer Daniel

Dept of Ophthalmology

Univ. of Pennsylvania

ebdaniel@upenn.edu

Gerhard Armauer Hansen Armauer Hansen 3 November 1879 Leprosy Hospital in Bergen Inoculated material taken from a leprous nodule into the eye of a female patient who probably suffered from borderline Leprosy according to the modern classification. Knut Blom Armauer Hansen and Human leprosy Transmission Medical Ethics and Legal Rights Int J Lepr Vol 41 (2)

Longitudinal Study of Ocular Leprosy

• Dr Paul Courtright

• India, Philippines, Ethiopia, Brazil

• Dr PSS Rao, Dr Ravenes, Dr Balagon

Patients

• New MB - Clinical Classification

• Active case finding - 301 patients

• 2 – year MDT, 5 – year RFT

• 2 Ophthalmic examinations every year

• Total follow up for 2 + 5 = 7 Years

Leprosy related ocular complications

At Diagnosis : 11%

During 2-year MDT: 9%

After MDT: 4% every year

1 in 5 Patients are likely to have a leprosy

related ocular manifestation

Prevalent Complications

Even with active case finding there is a considerable

amount of ocular pathology 11% present in newly

diagnosed MB patients.

Some of these are not amenable to medical treatment.

Every effort must be made to strengthen activities that promote early diagnosis and treatment of leprosy.

WHO ARE AT RISK FOR DEVELOPING OCULAR COMPLICATIONS?

The elderly patient

The smear positive patient

The badly deformed patient

Ocular Complications Occur After MDT

At the end of the MDT patients must be

educated regarding the possible risk of eye disease.

They should know about lagophthalmos, diminished

vision, red eye, or a facial skin patch in reaction.

Patients with lagophthalmos should continue to be

followed up.

FINDINGS FROM LOSOL Daniel E, ffytche TJ, Sundar Rao PSS, Kempen JH, Diener-West M, Courtright P. Incidence of ocular morbidity

among multibacillary leprosy patients during a 2 year course of multidrug therapy. Br J Ophthalmol. 2006;90:568-73.

Daniel E, ffytche TJ, Sundar Rao PSS, Kempen JH, Diener-West M, Courtright P. Incidence of ocular complications in patients with multibacillary leprosy after completion of a 2 year course of multidrug therapy.Br J Ophthalmol 2006;90:949-54.

Daniel E, Sundar Rao PS. Evolution of vision reducing cataract in skin smear positive lepromatous patients: does it have an inflammatory basis? Br J Ophthalmol. 2007;91:1011-3.

Daniel E, Koshy S, Rao GS, Rao PSSS. Ocular complications in newly diagnosed borderline lepromatous and lepromatous leprosy patients: baseline profile of the Indian Cohort. Br J Ophthalmol 2002;86:1336-40.

Courtright P, Daniel E, Rao PSSS, Ranenes J, Mengistu F, Belachew M, Celloria RV and ffytche T. Eye disease in multibacillary leprosy patients at the time of their leprosy diagnosis: findings from the Longitudinal Study of Ocular Leprosy (LOSOL) in India, the Philippines and Ethiopia. Lepr Rev 2002;73:225-238.

Daniel E, Sundar Rao PS, Ffytche TJ, Chacko S, Prasanth HR, Courtright P. Iris atrophy in patients with newly diagnosed multibacillary leprosy: at diagnosis, during and after completion of multidrug treatment. Br J Ophthalmol. 2007;91:1019-22.

Daniel E, Rao PS, Ffytche TJ, Courtright P. Ocular hypotension and hypotony in multibacillary leprosy patients; at diagnosis, during and after completion of multidrug therapy. Indian J Lepr. 2010;82:181-8

Patients and Ocular Complications Made up of clinically Diagnosed MB Patients.

No Paucibacillary (PB) patient controls: Would PB patients have shown lesser and less severe leprosy related ocular complications?

No Non-Leprosy controls: Would Non-leprosy ocular complications have been more in leprosy patients?

Rx has changed from 2 years to 1 year

LAGOPHTHALMOS

Early Diagnosis and Prevention: Recognizing risk factors Face Patch

Borderline Leprosy

Early MDT

Lagophthalmos: Medical Treatment

Aggressive Rx for erthymatous/depigmented face patches

Role of oral steroids: We will hear of this in a subsequent presentation by Dr Kamble

Newer tear substitutes Topical rebamipide: a derivative of quinolone-class

antibiotics - a mucin secretagogue

Marlowe SN, Hawksworth RA, Butlin CR, Nicholls PG, Lockwood DN. Clinical outcomes in a randomized controlled study comparing azathioprine and prednisolone versus prednisolone alone in the treatment of severe leprosy type 1 reactions in Nepal. Trans R Soc Trop Med Hyg. 2004;98:602-9.

Lagophthalmos: Surgery

• Surgical RX TMT advantages / Gold weight lid

implant • Role of Physiotherapy: Does adjuvant physiotherapy

help in recovery

Das P, Kumar J, Karthikeyan G, Rao PS. Efficacy of temporalis muscle transfer for correction of lagophthalmos in leprosy. Lepr Rev. 2011;82:279-85.

Corneal Sensory Loss in Leprosy Is it real and how important is it?

Corneal Sensation - The LOSOL Experience

Cotton wisp is not a good method in estimating corneal sensation

Longitudinal Study – Patient response to repeated corneal sensory testing

Clinic setting / Field setting

Corneal Sensation

Handheld esthesiometer - Cochet-Bonnet $500

Noncontact air puff technique Chemical stimulation using capsaicin Thermal stimulation with a carbon dioxide laser

Surrogate testing for corneal sensation?

Face Patch

Face anesthesia

Ct Dr Chandrasekhar

Ct Dr Margaret Hogeweg

Testing Corneal Sensation

CATARACT IN LOSOL 3 main ways to cataract: Age, Uveitis and Steroids INCIDENT CATARACT (<6/18) IN LOSOL PATIENTS Age (per decade): aHR = 2.50 (1.82-2.78) p < 0.001

Uveal involvement: aHR = 3.52 (1.42 to 8.67) p = 0.006

Grade 2 Deformity: aHR = 3.17 (1.12 to 8.97) p = 0.029

Oral Steroids were not associated All incident blindness related to cataract Surgery successful IOL >6/18 unaided vision

RESEARCH QUESTIONS RELATED TO CATARACT IN LEPROSY

Does cataract occur earlier and more in leprosy patients?

Do leprosy patients have good access to surgery?

RESEARCH QUESTIONS RELATED TO CATARACT IN LEPROSY

Is sub-clinical inflammation a problem with good vision outcomes after surgery?

1990. Recent advances in cataract surgery – how do they fare in leprosy patients?

ICCE, ECCE, Phacoemulcification - clear

corneal, SICS, Femtosecond laser, IOLs

Intractable Iridocyclitis

Increased oral steroids Subconjunctival injections of steroids Mycophenolate Mofetil, Azathioprine, Cyclosporine,

Methotrexate, Cyclophosphamide

Daniel E, Thorne JE, Newcomb CW, Pujari SS, Kaçmaz RO, Levy-Clarke GA, Nussenblatt RB, Rosenbaum JT, Suhler EB, Foster CS, Jabs DA, Kempen JH. Mycophenolate mofetil for ocular inflammation. Am J Ophthalmol 2010;149:423-32. Kaçmaz RO, Kempen JH, Newcomb C, Daniel E, Gangaputra S, Nussenblatt RB, Rosenbaum JT, Suhler EB, Thorne JE, Jabs DA, Levy-Clarke GA, Foster CS. Cyclosporine for ocular inflammatory diseases. Ophthalmology 2010;117:576-84 Pujari SS, Kempen JH, Newcomb CW, Gangaputra S, Daniel E, Suhler EB, ThorneJE, Jabs DA, Levy-Clarke GA, Nussenblatt RB, Rosenbaum JT, Foster CS. Cyclophosphamide for ocular inflammatory diseases. Ophthalmology 2010;117:356-65.

GRADING EYE COMPLICATIONS

Present WHO Grading of Hands and Feet Deformity

0 No anaesthesia: No visible deformity or damage

1 Anaesthesia present: No visible deformity or

damage

2 Visible deformity or damage present.

Present Eye Deformity Grading 0 No eye problems due to leprosy and no evidence of visual Impairment 1 Eye problems due to leprosy are present. Vision 6/60 or

better, The patient can count fingers at 6 meters. 2 Severe visual impairment (vision less than 6/60, the

patient is unable to count fingers at 6 meters), lagophthalmos, iridocyclitis and corneal opacities.

Problems with Present Eye Deformity Grading

Difficult to differentiate leprosy related eye problems from non-leprosy related eye problems: Cataract, Lagophthalmos, uveitis

Patients living longer with diseases associated with old age such as Diabetes and Hypertension can alter vision < 6/60 without obvious visible eye manifestations.

Do away with counting fingers at 6 meters? Manual for recording vision? Jean Watson. Evidence based practice.

Proposed Eye Deformity Grading 0 No visible eye manifestations. Patient visual

acuity ≥ 6/60

1 Visible eye manifestations present. Patient

visual acuity ≥ 6/60

2 Visible eye manifestations present or absent.

Patient visual acuity <6/60

Problems with the new proposed grading

No near vision estimation which is very

important to most patients

Will require carrying a near vision card and recording the near vision

BIOPSY SPECIMENS & THE ARMADILLO

Acknowledgements

P. Yowan, Padma Vijayakumari, C. Kumar, Maheshwari, Thirupurasundary, Shirley Chacko, Sheena Koshy

Timothy ffytche

Margaret Brand

Douglas Soutar