Ocular hypotension and hypotony in multibacillary leprosy patients; at diagnosis, during and after completion of multidrug therapy.

The prevalence and incidence of ocular hypotony (IOP < 7 mm Hg) and factors associated with them were determined in a Leprosy Referral Centre at Tamilnadu, India. Applanation intraocular pressures were measured every six months in a cohort of newly diagnosed multibacillary (MB) leprosy patients who were followed-up during the two year period of multidrug therapy (MDT) and for five years thereafter. Transient hypotony was present in two patients at the time of diagnosis, in 3 patients during MDT and in 9 patients after MDT with a cumulative prevalence of 4.65%. Transient ocular hypotension was present in 24 patients (8%) at disease diagnosis. 25 patients developed hypotension during MDT that was associated with trichiasis (HR 8.83 95% CI 2.06, 37.78 p = 0.003) and flare or/and cells (HR 4.60 95% CI 1.08, 19.64 p = 0.039). 29 patients developed ocular hypotension after MDT that was associated with punctate keratitis and uveal involvement. In general, MB leprosy patients with hypotension had a mean IOP of 12.60 mm Hg which differed significantly (p < 0.0001) from the mean IOP of 14.9 mm Hg in those who did not have hypotension. Transient hypotension and hypotony in MB leprosy patients are associated with signs of intraocular inflammation.

Incidence of ocular complications in patients with multibacillary leprosy after completion of a 2 year course of multidrug therapy.

AIM: To evaluate the incidence of and risk factors for ocular complications in multibacillary (MB) leprosy patients following completion of 2 year, fixed duration, multidrug therapy (MDT). METHODS: Biannual eye examinations were conducted prospectively on a cohort of MB patients who had completed MDT and followed up for 5 years. The incidence of ocular pathology was calculated as the number of events per person year of event free follow up of patients who did not have the specific finding before completion of MDT. RESULTS: 278 patients had one or more follow up visits after completion of MDT. The incidence of lagophthalmos was 0.24%/patient year (95% CI 0.10% to 0.37%); corneal opacity, 5.35%/patient year (95% CI 4.27% to 6.70%); uveal involvement, 3.78%/patient year (95% CI 2.96% to 4.83%); and cataract that reduced vision to 6/18 or less, 2.4%/patient year (95% CI 1.77% to 3.26%). Overall, 5.65%/patient year (95% CI 4.51% to 7.09%) developed leprosy related ocular disease and 3.86%/patient year (95% CI 3.00% to 4.95%) developed leprosy related, potentially blinding ocular pathology during the period following MDT. Age and other disability also predicted incident eye disease. CONCLUSIONS: Every year, approximately 5.6% of patients with MB who have completed MDT can be expected to develop new ocular complications of leprosy, which often (3.9%) are potentially vision threatening. Because many of these complications cannot be detected without slit lamp examination, periodic monitoring, particularly of older patients and those with other disability, is recommended, in order to detect and treat ocular complications satisfactorily.

Incidence of ocular morbidity among multibacillary leprosy patients during a 2 year course of multidrug therapy.

AIM: To evaluate the incidence of and risk factors for ocular complications in multibacillary (MB) leprosy patients during their 2 year, fixed duration, multidrug therapy (MDT). METHODS: Periodic eye examinations were conducted prospectively on a cohort of 301 consecutive newly diagnosed MB patients every 6 months during their 2 year course of MDT. Incidence of ocular pathology was calculated as the number of events per person year of event free follow up of patients who did not have the specific finding at baseline. RESULTS: 292 (97%) patients had one or more follow up visits. The incidence of lagophthalmos was 1.2%/patient year (95% CI 0.5% to 2.8%); corneal opacity was 7.4%/patient year (95% CI 5.1% to 10.6%); uveal involvement was 5.1%/patient year (95% CI 3.3% to 7.8%), and cataract that reduced vision to 6/18 or less was seen in 4.3%/patient year (95% CI 2.7% to 6.9%) of patients. Overall, 23 individuals (5.8%/patient year, 95% CI 3.9 to 8.8) developed leprosy related potentially blinding pathology during the 2 years of MDT. CONCLUSIONS: Approximately 20% of patients with MB leprosy can be expected to develop ocular complications of leprosy during a 2 year course of MDT, many (11%) of which are potentially vision threatening. Ophthalmological monitoring to detect and treat ocular complications at defined intervals during MDT is indicated.

Expression of protein gene product 9.5 in lepromatous eyes showing ciliary body nerve damage and a "dying back" phenomenon in the posterior ciliary nerves.

BACKGROUND/AIM: Peripheral nerve destruction is the hallmark of leprosy. Ocular complications form a substantial part of the clinical manifestations but histopathology of nerve destruction within ocular structures has not been shown satisfactorily. The role of protein gene product (PGP) 9.5 in identifying nerve destruction in the ciliary body and posterior ciliary nerves of lepromatous eyes is shown. METHODS: Serial sections from two lepromatous eyes and two non-lepromatous eyes were stained with PGP 9.5. Histopathological comparison was done on the expression of the PGP 9.5 stain in nerves within the ciliary body, posterior ciliary nerves adjacent to the optic nerve, and nerves tracking through the sclera. RESULTS: In non-lepromatous eyes, PGP 9.5 was expressed in nerves within the ciliary body, the nerves within the sclera, and posterior ciliary nerves adjacent to the optic nerve. In lepromatous eyes no PGP 9.5 was expressed, signifying nerve destruction. CONCLUSIONS: Nerve destruction in lepromatous eyes has been confirmed histopathologically by the absence of or patchy staining with PGP 9.5. Nerve destruction in the ciliary body can extend to the posterior ciliary nerves by an ascending axonopathy. This "dying back" phenomenon is akin to the "glove and stocking" anaesthesia found in lepromatous leprosy.

Are viable Mycobacterium leprae present in lepromatous patients after completion of 12 months' and 24 months' multi-drug therapy?

A study was carried out to determine whether or not viable bacilli persist in MB patients treated with 12-month and 24-month multidrug therapy (MDT). In the first group, 60 untreated lepromatous patients who had an initial average bacterial index (BI) of 3+ or more were enrolled. At the completion of 12 months of MDT, skin biopsies were obtained and M. leprae concentrate was inoculated into the footpads of five thymectomized and irradiated (T900r) mice. Rees technique was used for the mouse footpad (MFP) experiment. Harvesting was done it the 6th, 9th and 12th months. Out of the 60 biopsies inoculated into mouse footpads to check the viability of bacilli, 2 skin biopsies (3.3%) showed significant growth and 10 (16%) showed equivocal growth. 27 patients also had nerve biopsies tested for growth in MFP studies. None of the inoculated nerve biopsies showed significant multiplication in the MFP experiments. However, 4 biopsies (14%) showed equivocal growth. In the second group, 20 patients had skin biopsies and 10 had nerve biopsies done at the end of 24 doses of MDT in order to test the viability of bacilli; none of the skin or nerve biopsies from these patients showed any growth. This study showed that M. leprae present in the tissues after 24 doses of MDT are not viable and the drug schedule of 24 doses is adequate to treat leprosy patients, irrespective of their BI. However, a small (3.3%) percentage of the patients with a high BI harbour viable bacteria in the skin after 12 doses of treatment. Since a large majority of the patients (38 patients) who had a high initial BI responded well to the treatment, it is important to find out the reason for the lack of response in two patients. One of the reasons may be the presence of drug-resistant strains. It is important to follow up on these patients for a longer duration to ascertain whether or not they would relapse.

Ocular complications in newly diagnosed borderline lepromatous and lepromatous leprosy patients: baseline profile of the Indian cohort.

AIM: To describe ocular manifestations in newly diagnosed borderline lepromatous (BL) and lepromatous leprosy (LL) patients in India. METHODS: Ocular complications, at enrolment, occurring in all new borderline lepromatous and lepromatous leprosy patients detected by active case finding within the geographically defined leprosy endemic area of the Gudiyattam Taluk in India from 1991 to 1997 who consented to ocular examinations every 6 months, during and 5 years after treatment with multidrug therapy (MDT), were studied. RESULTS: Orbicularis oculi weakness (4.62%), lagophthalmos (4.20%), ectropion (0.42%), trichiasis (0.84%), blocked nasolacrimal ducts (1.68%), pterygium (11.34%), impaired corneal sensation (53%), corneal opacity (10.5%), corneal nerve beading (1.68%), punctate keratitis (1.26%), keratic precipitates (4.62%), iris atrophy (1.68%), and cataract (12.6%) were ocular complications seen in the 301 lepromatous patients at enrolment. 4.6% had blind eyes. Increasing age was associated with ocular complications. 80% of patients were skin smear acid fast bacilli (AFB) positive. The LL/BL ratio was 1:6.4. 71% had some limb deformity. 44% had only leprosy related ocular complications (LROC), 28% had only general ocular complications (GOC) while 14% had both LROC and GOC. Ocular complications were significantly related to leg deformities. Corneal nerve beading was seen most in LL patients (100%) having high bacterial content. Lagophthalmos and muscle weakness were associated with reversal reactions. CONCLUSIONS: Corneal nerve beading occurs in LL patients with high bacillary count. Patients with reversal reaction are more likely to present with orbicularis oculi weakness and lagophthalmos. Leprosy related ocular complications and general ocular complications are significant problems in newly diagnosed lepromatous patients. Elderly, deformed, skin smear positive, lepromatous patients are associated with increased ocular morbidity and form a group that require acceptable and accessible eye care.

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.

Existing prevalence surveys do not provide adequate information to estimate the magnitude of ocular pathology or vision loss in leprosy patients. We sought to determine the prevalence of ocular findings and related risk factors in leprosy patients at the time of their disease diagnosis. We also sought to determine if there were geographic differences and whether these were due to different demographic characteristics of the populations. The study was undertaken at Schieffelin Leprosy Research & Training Centre (Karigiri, India), Leonard Wood Memorial Leprosy Institute (Cebu, Philippines), and (for 3 years only) ALERT (Addis Ababa, Ethiopia). Newly diagnosed multibacillary (MB) leprosy patients as well as MB cases relapsed after dapsone monotherapy were eligible for enrollment. In each study site, the target population was 300. Standardized examinations were conducted between 1991 and 1998. Patient enrollment included 301 patients in Karigiri, 289 patients in Cebu, and 101 patients in Addis Ababa. The age-adjusted prevalence of blindness (< 6/60 in the better eye) and visual impairment (6/24-6/60) was 2.8% and 5.2%, respectively. Lagophthalmos and leprosy related uveal changes were detected in 3.3% (95% CI 2.0-4.7%) and 4.1% (95% CI 2.4-5.7) of patients, respectively. Overall, 11% (95% CI 8.5-13.2%) of newly enrolled MB patients had potentially blinding leprosy related ocular pathology. Lagophthalmos was associated with increasing age, a short duration between onset and diagnosis, and a previous reaction involving the face. Uveal conditions were associated with increasing age. Overall, eye disease was more common in Indian and Ethiopian patients compared to Filipino patients; however, differences were not significant when controlling for age and clinical (non-ocular) factors. Patients with potentially blinding leprosy related pathology were over three times more likely to have other (hand and foot) disabilities than patients without pathology. Differences in the prevalence of blindness and potentially blinding leprosy related ocular pathology between the sites could be accounted for by the differences in age and other clinical factors of the patients at the different sites. Findings suggest that, even in the face of active leprosy control efforts, around 11% of patients will have potentially blinding pathology at the time of their diagnosis and 2.8% will be blind. If those patients with lagophthalmos or blindness are considered appropriate for referral for more detailed assessment, approximately 4% of newly diagnosed leprosy patients will require active follow-up for eye care; including those with reaction involving the face will result in 9.4% of patients requiring active follow-up. These people are likely to be older, with a reaction involving the face, and/or with other disabilities than those not requiring active follow-up.

Ocular complications in newly diagnosed borderline lepromatous and lepromatous leprosy patients: baseline profile of the Indian cohort

Aim: To describe ocular manifestations in newly diagnosed borderline lepromatous (BL) and lepromatous leprosy (LL) patients in India. METHODS: Ocular complications, at enrolment, occurring in all new borderline lepromatous and lepromatous leprosy patients detected by active case finding within the geographically defined leprosy endemic area of the Gudiyattam Taluk in India from 1991 to 1997 who consented to ocular examinations every 6 months, during and 5 years after treatment with multidrug therapy (MDT), were studied. RESULTS: Orbicularis oculi weakness (4.62 per cent), lagophthalmos (4.20 per cent), ectropion (0.42 per cent), trichiasis (0.84 per cent), blocked nasolacrimal ducts (1.68 per cent), pterygium (11.34 per cent), impaired corneal sensation (53 per cent), corneal opacity (10.5 per cent), corneal nerve beading (1.68 per cent), punctate keratitis (1.26 per cent), keratic precipitates (4.62 per cent), iris atrophy (1.68 per cent), and cataract (12.6 per cent) were ocular complications seen in the 301 lepromatous patients at enrolment. 4.6 per cent had blind eyes. Increasing age was associated with ocular complications. 80 per cent of patients were skin smear acid fast bacilli (AFB) positive. The LL/BL ratio was 1:6.4. 71 per cent had some limb deformity. 44 per cent had only leprosy related ocular complications (LROC), 28 per cent had only general ocular complications (GOC) while 14 per cent had both LROC and GOC. Ocular complications were significantly related to leg deformities. Corneal nerve beading was seen most in LL patients (100 per cent) having high bacterial content. Lagophthalmos and muscle weakness were associated with reversal reactions. CONCLUSIONS: Corneal nerve beading occurs in LL patients with high bacillary count. Patients with reversal reaction are more likely to present with orbicularis oculi weakness and lagophthalmos. Leprosy related ocular complications and general ocular complications are significant problems in newly diagnosed lepromatous patients. Elderly, deformed, skin smear positive, lepromatous patients are associated with increased ocular morbidity and form a group that require acceptable and accessible eye care.

Nocardia farcinica pleuritis in a lepromatous patient with severe necrotizing reaction: an unusual presentation.

A young, male, lepromatous leprosy patient with a severe necrotizing erythema nodosum leprosum reaction treated with prolonged oral steroids and thalidomide developed pleuritis that was caused by a rare opportunistic pathogen, Nocardia farcinica. This organism was resistant to most antibiotics but was susceptible to amikacin and minocycline. During the course of treatment the patient developed severe gastritis which necessitated the removal of clofazimine and the inclusion of an H2 receptor antagonist. Bilateral steroid-induced cataracts needed surgical correction. This case is being presented for its rare opportunistic bacterial infection and for the multiple complications which made treatment difficult.

Pathogenesis of dry eye in leprosy and tear functions.

Seventy-five leprosy patients and an equal number of age- and sex-matched controls were examined for tear functions, using Schirmer's test and tear break up time (BUT). There was no statistically significant difference in the Schirmer's test, but the tear BUT showed a statistically significant lower value of < 10 seconds in multibacillary patients compared to paucibacillary patients. Leprosy patients with lagophthalmos and decreased corneal sensation showed a lower value of tear BUT which was also statistically significant. This study shows that even though the quantity of tears is not affected, proper and prolonged wetting of the cornea is deficient in many leprosy patients.

Epithelioid granuloma in the iris of a lepromatous leprosy patient; an unusual finding.

This case report depicts a case of histopathologically confirmed polar lepromatous (LL) leprosy with a bacterial index of 4+. He experienced recurrent episodes of erythema nodosum leprosum (ENL) in the first 5 years after diagnosis. Skin smears became negative after 6 years of dapsone monotherapy and have remained negative since that time. At 23 years after diagnosis, the patient had developed cataracts and underwent intracapsular cataract extractions with broad-based iridectomies. In one of the iris specimens, histopathologic examination revealed a focal granuloma composed of epithelioid cells. Subsequently a lepromin skin test showed a positive Mitsuda reaction with a borderline tuberculoid histopathology. This clearly illustrates the immunological upgrading of a polar lepromatous patient, perceived first in the iris tissue.

Pathology of a lepromatous eye.

Histopathological examination of an enucleated eye from a lepromatous leprosy patient showed the cornea, ciliary body, and part of the choroid to be infiltrated by macrophages filled with Mycobacterium leprae. The walls of blood vessels in the sclera, ciliary body and the anterior choroid demonstrated the presence of M. leprae, giving credence to the blood-borne entry of M. leprae into the eye. Unlike the eyes of experimental animals infected with M. leprae, histopathological study of this eye from a lepromatous leprosy patient demonstrated that M. leprae, although demonstrable in the anterior choroid, could not be found in the posterior parts of the eye, substantiating the claim that leprosy does not affect the posterior parts of the eye directly.

Infectious keratitis in leprosy.

AIM: To describe leprosy characteristics, ocular features, and type of organisms that produce infective corneal ulcers in leprosy patients. METHOD: The records of all leprosy patients admitted for treatment of corneal ulcers between 1992 and 1997 were reviewed. RESULTS: 63 leprosy patients, 53 males and 10 females, are described. 16 were tuberculoid and 47 lepromatous. 25 patients had completed multidrug therapy. 10 patients had face patches, eight had type I reaction, and 10 had type II reaction. 43 (68%) patients had hand deformities. In 54% of patients pain was absent as a presenting symptom. 19 patients gave a history of trauma. In 15 patients ulcers had also occurred on the other eye, five of them having occurred during the study period and the rest before 1992. Of the 68 eyes with corneal ulcers, 28 had madarosis, 34 had lagophthalmos, nine had ectropion, three had trichiasis, six had blocked nasolacrimal ducts, and 39 decreased corneal sensation. In 14 eyes, a previous lagophthalmos surgery had been done. 16 patients were blind at presentation. 32% of ulcers were located centrally. After treatment only 18% of the eyes showed visual improvement. Five types of fungus were cultured, two of them rare ocular pathogens. CONCLUSIONS: Corneal ulcers occur more in males and in the lepromatous group of patients. Decreased corneal sensation, lagophthalmos and hand deformity are closely associated. Indigenous treatment and late presentations were notable in many patients. Visual outcome is not good. There is increased risk of developing an ulcer in the other eye. Fungal corneal ulcers are not uncommon.

Hypopigmented face patches; their distribution and relevance to ocular complications in leprosy.

Eighty-two leprosy patients with hypopigmented patches over the face (cases) and an equal number of age-, sex-, and classification-matched leprosy patients without any hypopigmented patches over the face (controls) were examined for the distribution of hypopigmented facial patches, areas of anesthesia over the face, and eye complications. The hypopigmented patches did not follow any pattern and overlapped in the areas of sensation supplied by the three branches of the trigeminal nerve. Anesthesia over the face, evaluated by a Semmes-Weinstein monofilament which exerted a force of 0.05 grams, was present in 19.5% of the cases and 15.9% of the controls. Patients with hypopigmented facial patches were found to have more corneal hypoesthesia than patients who did not have hypopigmented facial patches. The risk of having impaired corneal sensation was three to four times higher in patients with hypopigmented facial patches. This feature can be used to identify decreased corneal sensation among leprosy patients under field conditions where direct estimation of corneal sensation is not advocated.