Br J Ophthalmol: first published as 10.1136/bjo.65.7.494 on 1 July 1981. Downloaded from

British Journal ofOphthalmology, 1981, 65, 494-502

Ocular changes with oral and transepidermal diethylcarbamazine therapy of

HUGH R. TAYLOR' AND BRUCE M. GREENE2 From the 'International Center for Epidemiologic and Preventive , Wilmer Ophthalmological Institute, Johns Hopkins Medical Institutions, Baltimore, Maryland 21205, USA, and the 2Division of Geographic Medicine, Department of Medicine, Case Western Reserve Ujniversity and University Hospitals, Cleveland, Ohio 44106, USA

SUMMARY Twenty men with moderate infection of Onchocerca volvulus were studied in a double- masked, controlled clinical trial to compare the safety and efficacy of oral diethylcarbamazine (DEC) with topical DEC lotion. Visual acuity and colour vision did not alter during the 6 months of observation, although 2 patients receiving DEC lotion and 3 patients receiving oral DEC developed either visual field constriction or optic atrophy. Fluffy corneal opacities were common in both groups. Intraocular microfilariae also appeared in both groups but to a greater extent in those receiving DEC lotion. New chorioretinal changes developed in 4 men receiving lotion and in only 1 receiving tablets. It is concluded that DEC lotion offers no advantage over tablets in the treatment of ocular onchocerciasis and in fact may be associated with more ocular complications than the conventional oral treatment.

Onchocerciasis, or river blindness, is the disease treatment of people with onchocerciasis frequently caused by the filarial parasite Onchocerca volvulus. It causes serious systemic, dermal, and ocular side http://bjo.bmj.com/ is characterised by the presence of relatively few adult effects. worms encapsulated in subcutaneous nodules and Although DEC is readily absorbed when given by invasion of the body, especially the skin and the eyes, mouth, its transepidermal application also has been by millions of microfilariae. The main disability advocated.5 DEC citrate is absorbed by the skin, and caused by onchocerciasis is blindness, either from in theory the transepidermal application should pro- corneal or chorioretinal scarring, or from the sequelae vide a therapeutic concentration of the drug in the

of anterior . The pathological changes seen skin, where most of the microfilariae reside, with on September 24, 2021 by guest. Protected copyright. with onchocerciasis appear to be related directly or minimal systemic absorption. It was hoped that a indirectly to the death of microfilariae. reduction in systemic absorption would lead to a While recent efforts have resulted in an improved decrease in systemic and ocular side effects. understanding of the clinical presentation and natural A recently reported double-masked, controlled history of onchocerciasis, methods of treating the clinical trial evaluated the safety and efficacy of oral disease remain unsatisfactory. Suramin sodium is the DEC and topical DEC in Liberian males with only clinically acceptable drug that kills the adult moderate infections of 0. volvulus.3 This study worms of Onchocerca volvulus. Its usefulness, how- showed that topical DEC was not only less effective ever, is severely limited because it must be given intra- than oral DEC in reducing the number of micro- venously, and it has a number of toxic side effects.' filariae in skin snips, but that topical DEC therapy Diethylcarbamazine (DEC), on the other hand, has was accompanied by at least as many systemic side relatively few intrinsic toxic side effects.2 But, effects as oral DEC, if not more. Despite this, it has although it promotes killing of microfilariae in vivo, it been suggested that the use of topical DEC may have has no demonstrable effect on adult worms.3 In some role in the reduction ofintraocular microfilariae.6 addition, as initially described by Mazotti,4 DEC The purpose of this report is to present in detail the Correspondence to Hugh R. Taylor, MD, Johns Hopkins Hospital, ocular changes observed in a double-masked con- Wilmer Institute, Woods Research Bldg., Room 261, Baltimore, trolled trial which compared oral and transepidermal Maryland 21205, USA administration of DEC. 494 Br J Ophthalmol: first published as 10.1136/bjo.65.7.494 on 1 July 1981. Downloaded from

Ocular changes with oral and transepidermal diethylcarbamazine therapy of onchocerciasis 495

Materials and methods TREATMENT PROTOCOL The patients were randomised into 2 groups in a SUBJECTS double-masked fashion. One group, called the 'tablet Twenty male employees of the Firestone Plantation group', received DEC citrate tablets (50 mg tablet, Company, Harbel, Liberia, were selected on the basis Lederle Laboratories, Valley Stream, NY) and of their having a moderate infection with 0. volvulus, placebo lotion (Nivea lotion, Biersdorf, South as determined by skin-snip microfilariae count, Norwalk, Conn.). The other group, called the 'lotion without having significant or other group', received a placebo tablet (Lederle), and 2% significant illness. The methodology used in this study DEC lotion made by adding powdered DEC citrate has been described in detail elsewhere.3 to the Nivea lotion to make a 2% (w/v) preparation. On the first day of therapy all patients received 1 CLINICAL EXAMINATION tablet, either DEC or placebo, and 15 ml of lotion, A detailed ophthalmological examination was per- either placebo or DEC. The lotion was applied to the formed, including visual acuity, confrontation visual whole body except to the scalp and the soles of the fields (with a 0-8 cm diameter red target), colour feet. For the next 7 days tablets were given 3 times vision (AO pseudoisochromatic plates), and pupillary daily and lotion once daily after a bath. From the response. After head-down posturing, the and second week patients were given tablets and lotion on anterior chamber were examined with a Haag-Streit only 1 day a week. During the first 2 months 3 tablets Series 900 slit-lamp for the presence of microfilariae, were taken in 3 divided doses on 1 day a week (total corneal changes, and uveitis. Intraocular pressure dose, 150 mg), and for the last 4 months 4 tablets were was measured with a pneumatonometer. Mydriatic given in 2 divided doses (total dose, 200 mg). Medica- direct and indirect were performed. tion was taken or applied under direct supervision. Colour photographs of the and other fundal structures were taken with a Kowa fundus camera, Results and external ocular photographs were taken with a 35 mm camera with a macro . GENERAL FEATURES Patients were admitted to hospital for the first 2 Randomisation produced 2 groups that closely weeks of treatment. The ophthalmic and general resembled each other. The men in the 2 groups were physical examinations were performed before treat- of similar age (mean age for the lotion group was ment and again at 1, 3, 7, and 14 days, and at 2 and 6 39-8±11-2 years and for the tablet group 37-4+14-3 months after the start of treatment. Skin snips also years) and had comparable involvement with http://bjo.bmj.com/ were taken at these times to determine the micro- onchocerciasis (Table 1). All patients had palpable filarial density in the skin. nodules. The geometric means of microfilarial counts

Table I Summary ofimportant ocular changes seen in 20 men enrolled in a double-masked trial comparing DEC lotion with DEC tablets

Patient Pretreatment Intraocular Fluffy corneal Pretreatment New Visualfield Other comments on September 24, 2021 by guest. Protected copyright. number sclerosing mfat 6 months opacities chorioretinal chorioretinal pallor constriction at 6 months changes changes DEC lotion I + + + + + Penetrating injury, OD 2 + 6 + + + + X +4+ + + + 10 + + + + + Colour blind (congenital) 11 + + 14 16 + + + + . vitritis 17 ++ + 20 + + DEC tablets 3 + + + 4 + + 5 + 7 + 9 + + 12 + + + 13 15 + + 18 19 + + + + + + Limbitis Br J Ophthalmol: first published as 10.1136/bjo.65.7.494 on 1 July 1981. Downloaded from

496 Hugh R. Taylor and Bruce M. Greene

30O 20. Fig. I The geometric means ofthe mean microfilarial count in skin CL 15- snipsfrom the 10 persons receiving 10- DEC tablets and the 10 persons receiving DEC lotion for 6 months z 4 plotted on a semilog scale. Luw Error bars indicate the standard error ofthe mean. For comparison, 0 the pretreatment arithmetic 2- mean (±standard deviation) was w 24-3 (+10 0) for the tablet group uC 1-. and 29-8 (± 16-0) for the lotion 0.5- group. 0.2 1 WEEK 2 MONTHS 4 MONTHS 6 MONTHS

before treatment were 16-7 microfilariae per skin snip constriction of the superior field in the left eye was for the prospective DEC lotion group and 14- 1 for the noticed at 14 days. At 2 months the fields were con- prospective DEC tablet group. Mean microfilarial stricted to 20 degrees in the left eye and 5 to 10 skin-snip counts for both groups fell during therapy degrees in the right. In the left eye the inferonasal (Fig. 1); however, the count for those receiving DEC quadrant seemed to be relatively spared. At 6 months tablets fell more rapidly and to a lower level. there was generalised constriction to 10 to 15 degrees in each eye. In the third patient who received DEC VISUAL ACUITY AND COLOUR VISION lotion (patient 16) visual fields were noted to be full at Before treatment all men had normal visual acuity the pretreatment examination and again at 2 weeks (better than 6/12 with or without refraction), with the and at 2 months. However, at 6 months visual fields in exception of 1 man in the lotion group (patient 1). He both eyes were found to. be constricted to 5 to 10 had sustained a penetrating injury to the right eye 3 degrees. years which reduced the vision in that eye previously http://bjo.bmj.com/ to hand movements. There was no change in visual PUPILLARY RESPONSES acuity noted in any person in either group during the were in 6-month period of treatment. Pupillary responses normal all patients before treatment with the exception of 1 man in the lotion All men had normal colour vision with the excep- group (patient 16) who had anisocoria with a mildly tion of 1 patient in the lotion group (patient 10), who miotic right . No change was observed in the had a bilateral defect in the recognition of red-green pupillary reactions in this patient or in any other at the pretreatment examination. This defect was thought to be congenital. No change in colour vision patient during this study. on September 24, 2021 by guest. Protected copyright. was noticed in any person during the period of observation. INTRAOCULAR MICROFILARIAE Before treatment microfilariae were not observed in VISUAL FIELDS the cornea or anterior chamber of any patient in Confrontation visual fields were full in all men at the either group. During the first 2 weeks of treatment start of treatment. During the course of treatment microfilariae were seen commonly in the eyes of visual field constriction was noted in 2 men who people in both groups (Fig. 2A). However, at both 2 received DEC tablets and in 1 man who was receiving and 6 months only 2 people receiving DEC tablets DEC lotion. One of the patients receiving tablets had intraocular microfilariae, while 6 people receiving (patient 12) had a constriction of the superior field in DEC lotion did. During the 6 months of observation the right eye 14 days after the start of treatment. At 2 all 10 people receiving DEC lotion had intraocular months the visual fields of both eyes were constricted. microfilariae detected at some time, whereas only 7 of Goldmann perimetry showed a reproducible those receiving DEC tablets did. Five people receiving symmetrical constriction to 20 degrees with a 4/V lotion had microfilariae on 4 or more of the 6 eye white target. At 6 months the field in the right eye was examinations, whereas only 2 people receiving tablets reduced to 5 and 10 degrees of fixation, and there was did: none had intraocular microfilariae before treat- loss of the inferior field to 10 to 20 degrees in the left. ment. The mean number ofmicrofilariae in the cornea In another patient receiving DEC tablets (patient 19) and in the anterior chamber also was greater in those Br J Ophthalmol: first published as 10.1136/bjo.65.7.494 on 1 July 1981. Downloaded from

Ocular changes with oral and transepidermal diethylcarbamazine therapy of onchocerciasis 497

10 A DEC TABLETS - w DEC LOTION 0 - - C -J 0-0 8- a.w o 6 or\i----_------I Ii/ wm 4- I 2- I~~

1 2 3 4 5 6 MONTHS

20 DEC TABLETS * * Fig. 2 A. The number ofpeople B " DEC LOTION 0- - - C _0 with intraocular microfilariae. " B. The mean number of mu< 1 5- N _- ~~ NXNN - - ~microfilariae in the anterior chamber in those with intracameral Z ° o zoz 10- 9l 0-- - microfilariae. C. The mean number 60 ofmicrofilariae in the cornea in those with intracorneal 0 microfilariae. There were 10 men in _ each group, and they were 2 3 4 5 6 examined during 6 months of treatment. MONTHS

< 20 DEC TABLETS D1 C * J - DEC LOTION ---C m > 155 - http://bjo.bmj.com/ z o Z C) 1 0 0_ A_~~~~A O 5 S ~ ~~~~~~~~~~~~------I

1 2 3 4 5 6 on September 24, 2021 by guest. Protected copyright. MONTHS receiving DEC lotion than in those receiving tablets patients in the tablet group and 2 patients in the lotion (Figs. 2B and C). group had 'haze' in the peripheral cornea, which was most marked in the nasal and temporal areas in the KERATITIS interpalpebral fissure. This is regarded as the earliest Punctate keratitis (fluffy or snowflake comeal slit-lamp sign of sclerosing keratitis. No change or opacities) was present in 1 patient in each group progression of sclerosing keratitis was noticed during before treatment. During treatment it appeared in a the study in men in either group. further 6 patients receiving DEC lotion and in 7 patients receiving DEC tablets. Most fluffy opacities LIMBITIS were seen during the first 2 weeks (Fig. 3A). At 6 One patient receiving DEC tablets (patient 19) months, however, 5 patients receiving DEC lotion developed severe limbitis and bulbar conjunctival still had fluffy opacities, although they were seen in chemosis on the day after starting oral DEC. This had only 1 patient receiving DEC tablets at this time. almost entirely disappeared by 14 days. Despite Before the start of treatment early sclerosing careful examination the specific globular limbitis keratitis was present in 2 patients in the tablet group described as occurring during the treatment of and 3 patients in the lotion group. An additional 3 onchocerciasis with DEC was not observed.7 Br J Ophthalmol: first published as 10.1136/bjo.65.7.494 on 1 July 1981. Downloaded from

498 Hugh R. Taylor and Bruce M. Greene

a--J 0 w cL LL 0 cr

z

Fig. 3 A. The number ofpeople withfluffy corneal opacities. B. The MONTHS number ofpeople with anterior uveitis. There were 10 men in each group, and they were examined w during 6 months oftreatment. a.-J DEC TABLETS 0-* 0 8 w DEC LOTION O----O 0* LL 0 6- w 4- --o D z 2-

2 3 4 5 6 MONTHS

ANTERIOR UVEITIS demonstrated on the stereo colour photographs, nor http://bjo.bmj.com/ Anterior uveitis, as determined by the presence of was there a change in his visual fields or colour vision. cells or a flare in the anterior chamber, was not found The cup:disc ratio remained at 0-2 on the right and 0 3 in any patient before treatment. Within 7 days of the on the left throughout this study. One patient receiv- start of therapy, however, 6 patients in each group ing DEC lotion (patient 10) had questionable pallor had developed signs of anterior uveitis. In only 1 of his discs at 2 months, and at 6 months he had patient in each group was this more severe than a mild definite generalised pallor of both discs. Again no uveitis (patients 15 and 16). After the first week of change could be detected in the photographs of the on September 24, 2021 by guest. Protected copyright. treatment anterior uveitis was seen in fewer people discs-in particular, a small pre-existing infero- receiving oral DEC than in those receiving lotion, so temporal nerve fibre loss in the right eye remained that at 2 months only 3 of the tablet group had mild unchanged during this period. Similarly, there was no uveitis, whereas 7 patients receiving DEC lotion did change in his visual fields nor in the cup:disc ratio, (Fig. 3B). which remained at 0-6 in both eyes. This patient had defective colour vision at the start of treatment, and OPTIC DISC CHANGES this showed no change during the study. The other Before the commencement of treatment the optic patient, who showed optic disc changes while being discs of all patients were considered normal. In 1 treated with DEC lotion (patient 16), also showed a patient (patient 1) the optic disc of the right eye could generalised pallor of both discs. This was first noted at not be examined because of the presence of a 6 months, although, again, no changes were detected traumatic . During the study definite changes in the photographs of the discs nor in the patient's were seen in the optic nerve of 2 men (both receiving colour vision. There was, however, marked visual DEC lotion), and questionable changes were seen in field constriction. The visual fields in each eye, which a third (treated with DEC tablets). had been full up to 2 months, were constricted to 5 to The patient receiving DEC tablets (patient 7) was 10 degrees at 6 months when the disc pallor was seen. thought to have questionable pallor of the optic nerve This patient had pre-existing anisocoria with head of each eye at 6 months. No changes could be of the right pupil, and bilateral vitritis which became Br J Ophthalmol: first published as 10.1136/bjo.65.7.494 on 1 July 1981. Downloaded from

Ocular changes with oral and transepidermal diethylcarbamazine therapy of onchocerciasis 499 more severe during the study. The optic nerve of each progressed to a chorioretinal scar at 6 months. New eye showed no cupping during the period of observa- areas of chorioretinal scarring developed in 4 men tion. receiving lotion (patients 6, 8, 10, and 17). Two of the In the other 2 men who showed visual field constric- men who developed these changes (8 and 17) had tion (patients 12 and 19) optic nerve examination normal fundal examinations before treatment, and remained normal throughout the study, and there the new lesions were their first evidence of posterior were no changes in the cup:disc ratios. Further, there segment disease. The other 3 men had pre-existing was no change in the photographic appearance of the chorioretinal lesions. The patient with pre-existing nerve heads. vitritis (patient 16) developed moderately dense vitreous opacities during treatment. Pre-existing chorioretinal changes attributable to INTRAOCULAR PRESSURE onchocerciasis were present in 5 men who were to The mean intraocular pressure for each group receive DEC lotion and in 6 who were to receive DEC showed no significant change during the course of tablets. In 3 men receiving DEC tablets (patients 3, 5, treatment. Further, no significant rise or fall in and 9) and in 4 receiving DEC lotion (patients 1, 2, 6, pressure was observed in any individual in either and 10) this took the form of peripheral chorioretinal group. scarring, although in I patient (patient 1) this was associated with marked retinal pigment epithelial Discussion atrophy in the macular area. One man in the lotion group (patient 16) had bilateral vitritis, bilateral The ocular changes seen with the DEC treatment of peripheral chorioretinal scars, and epiretinal mem- onchocerciasis have been well described.8 They branes in the left macular region. A posterior polar include a dramatic increase in the number of intra- chorioretinal scar was present in 1 patient receiving corneal microfilariae and the appearance of punctate DEC tablets (patient 4), peripapillary atrophy keratitis (fluffy opacities), which are seen when the occurred bilaterally in another receiving DEC tablets microfilariae in the cornea die. These opacities, (patient 19), and a glial proliferation was present in a which clear over a period of time, are formed by the third (patient 15). acute inflammatory infiltrate which surrounds dead During this study new chorioretinal lesions de- and dying microfilariae.9 A marked increase in the veloped in a total of 5 men. A focal area of acute number of microfilariae in the anterior chamber with chorioretinitis was observed at 2 months in 1 man the initiation of treatment and the development or http://bjo.bmj.com/ receiving DEC tablets (patient 3) (Fig. 4). This had exacerbation of anterior uveitis are also well recog- nised. Thus, one effect of DEC therapy on micro- filariae seems to be to activate or mobilise them, which results in microfilariae being 'driven' into the eye. With time, however, there is usually a reduction in the number of microfilariae in the eye, and there is a temporary improvement of lesions in the anterior on September 24, 2021 by guest. Protected copyright. segment. There appears to be little change, however, in the progression of posterior lesions.8 The conclusions drawn from any clinical trial must be considered in the context of the methodology employed. This study was double-masked, so that neither the investigators nor the patients were aware of which treatment a particular patient was receiving. The code was not broken until all clinical and labora- tory studies were completed. The randomisation used in this study produced 2 groups of men that were highly comparable before the start of treatment. Not only were the microfilarial counts similar in each group, but the ocular examination in terms of scleros- ing keratitis, anterior uveitis, and chorioretinal changes was also comparable. Fig. 4 A focal area ofactive chorioretinitis observed in a The presence of intraocular microfilariae is strongly man who had been treated with oral DECfor 2 months correlated with the severity of onchocercal lesions (patient 3). and the risk of developing blindness.'0 It is note- Br J Ophthalmol: first published as 10.1136/bjo.65.7.494 on 1 July 1981. Downloaded from

500 Hugh R. Taylor and Bruce M. Greene worthy in this regard that intraocular microfilariae pigment epithelium. Both the optic nerve changes were not present in either group before treatment. and the retinal pigment epithelial changes could be Although microfilariae appeared in both the cornea recognised only by fluorescein angiography. Neither and the anterior chamber of members of both groups. of these could be observed during the present study the number of people with intraocular microfilariae, because fluorescein angiography was not used. Con- the time microfilariae stayed in the eye, and the versely, optic atrophy developed in 3 patients in our absolute counts of microfilariae, both in the cornea study but is not considered in the study of Bird and and the anterior chamber, were higher in those co-workers, as their follow-up was for only 8 days. Of receiving DEC lotion than in those receiving DEC particular concern in the present study is the fact that tablets. In particular, at 2 and 6 months microfilariae visual field constriction and optic atrophy developed were still present in the eyes of more than half the as commonly in people who received DEC lotion as in patients receiving DEC lotion. those who received tablets. Although microfilariae appeared in both the The transepidermal application of DEC as a lotion anterior chamber and the cornea during DEC lotion has been advocated as a way of eliminating systemic therapy, the greatest migration was into the anterior absorption, thus preventing ocular and systemic re- chamber. Another study, examining the effect of the actions.56 Serum levels of DEC in patients receiving DEC lotion on intraocular microfilariae, showed an DEC lotion are less than one-tenth of those found in apparent reduction in intracameral microfilarial patients receiving DEC tablets.3 However, sufficient counts in people receiving the lotion." As the drug appears to be absorbed to initiate the complex authors point out, the ophthalmic examinations in and as yet undefined series of events that have this previous study were conducted by a number of plagued the clinical use of oral diethylcarbamazine in different observers, and therefore their findings onchocerciasis, resulting in both systemic and ocular relating to intraocular microfilariae must be regarded side effects, including optic atrophy. with circumspection." The present study, however. The death of microfilariae in the cornea and the shows quite clearly that DEC lotion 'drives' micro- development of fluffy corneal opacities are direct filariae into the eye, especially into the anterior evidence that microfilariae are dying inside the eye. chamber, to an even greater extent than does oral This strongly suggests that DEC lotion kills intra- DEC. ocular microfilariae, and indicates that the effect of Evidence of optic nerve involvement, that is, visual DEC lotion is not limited to the skin. However, it field constriction and/or optic nerve pallor (optic must be acknowledged that there is the remote possi- atrophy), occurred with approximately equal bilitv that microfilariae lethally damaged by DEC http://bjo.bmj.com/ frequency in each group. The generalised constric- could migrate into the cornea and subsequently die. tion of visual fields to 5 -to 10 degrees has been An increase in the number of people with anterior described as a common finding in patients with uveitis was noticed in both groups. For the most part onchocerciasis, and visual acuity usually is not the anterior uveitis was relatively mild. However, reduced.'2 Similar visual field defects also have been uveitis developed more frequently and was more reported as occurring acutely during oral DEC persistent in those who received DEC lotion. The treatment. 13 pathogenesis of uveitis is not clear, but it is possible on September 24, 2021 by guest. Protected copyright. Optic atrophy has long been viewed as part of the that it is related to the presence of circulating immune clinical picture of onchocerciasis. Recently, however. complexes which could cause vasculitis and subse- a number of reports have suggested an association quent leakage ofserum proteins and cells from vessels between optic atrophy and the use of onchocerciasis into the anterior chamber. It should be noted that chemotherapy. 13 1' In a study in the Cameroons proteinuria has been reported as developing with Anderson and co-workers found that 3 of 18 people DEC therapy and is seen more commonly with DEC treated with oral DEC developed optic atrophv. and lotion. 6 It is interesting, therefore, to note that the 6 of another 21 people showed some changes in the development of proteinuria appears to be correlated appearance of the optic nerve during DEC treat- with the presence of circulating immune com- ment.8 The risk of optic atrophy was similar in plexes.'" and it may be that a similar mechanism is another study in which combined therapy, consisting involved in causing uveitis. of DEC followed by suramin, was used. ' Using The development of an area of acute focal chorio- fluorescein angiography Bird and co-workers'3 in a patient receiving DEC tablets was found acute in 9 of II people receiving especially interesting, as we are not aware of a similar oral DEC and an aggravation of fluorescein leakage lesion having been previously reported as a result of in 4 of a further 10 patients who had pre-existing DEC treatment. It is impossible to tell whether this leakage. They also demonstrated the frequent de- lesion occurred because of, or in spite of, the con- velopment of acute self-limiting lesions of the retinal current use of DEC. This active lesion developed in Br J Ophthalmol: first published as 10.1136/bjo.65.7.494 on 1 July 1981. Downloaded from

Ocular changes with oral and transepidermal diethylcarbamazine therapy of onchocerciasis 501 an eye which already had evidence of onchocercal tissues.6 In fact the use of the lotion caused the chorioretinitis, as did the new lesions in 2 patients appearance of increased numbers of intraocular receiving DEC lotion. It should be noted, however, microfilariae and was attended by even more ocular that new chorioretinal lesions developed in another 2 changes than seen with oral DEC. people who were receiving DEC lotion and who did not have pre-existing chorioretinal lesions. While We thank the Firestone Plantations Company, Harbel, Liberia these probably were not due to a of the (under the direction of Mr R. C. Larson), Drs Z. D. Traub and E. direct effect Jallah, Mary and Willem Kraaij, Jennifer Dennis, Carol Vispo, and DEC lotion, the use of the lotion certainly did not other personnel of the Firestone Medical Center and Plantations prevent their appearance. Company, and Drs M. Del Monte and M. E. Langham, of the Johns Several authors have commented on an apparent Hopkins University, for their co-operation and support. association of onchocerciasis and , par- This work was supported by research grants from the Rockefeller Foundation, New York, and from the Firestone Tire and Rubber ticularly juvenile glaucoma, in certain areas of Company, Akron, Ohio, and by NIH grants BRS 16-80 and Africa.'8 19 This led to speculation of a causal EY-03318. relationship of onchocerciasis to glaucoma and to the suggestion that intraocular pressure was lowered by References DEC treatment.5 More recently, an extensive study has shown that people with onchocerciasis have, if I Anderson J, Fuglsang H, Marshall TF. Effects of suramin on lower intraocular than ocular onchocerciasis. Tropenmed Parasitol 1976; 27: 279-96. anything, pressures people 2 Hawking F. Diethylcarbamazine and new compounds for the without onchocerciasis, except for the few people treatment of filariasis. Adv Pharmacol Chemother 1979; 16: who develop secondary glaucoma following severe 129-94. uveitis.20 No one in the present study had a raised 3 Taylor HR, Greene BM, Langham ME. Controlled clinical trial intraocular pressure, and there was no of oral and topical diethylcarbamazine in treatment of significant onchocerciasis. Lancet 1980; i: 943-6. decrease in pressure over time. These findings would 4 Mazzotti L. Possibilidad de utilizar como medio diagnostico support the contention that onchocerciasis per se auxiliar en la oncocercosis, las reacciones alergicas consecutivas a does not elevate intraocular pressure. la administracion de 'Hetrazan'. Rev Inst Salubr Enferm Trop In conclusion, during this study all of the major (Mex) 1948; 9:235-7. 5 Langham ME, Traub ZD, Richardson R. A transepidermal ocular side effects described as occurring with oral chemotherapy of onchocerciasis. Tropenmed Parasitol 1978; 29: DEC were seen with both topical and oral DEC 156-62. therapy, with the exception of globular limbitis. The 6 Langham ME. Diethylcarbamazine lotion in onchocerciasis. more subtle changes in the retinal pigment epithelium Lancet 1980; i: 977-8. 7 Jones BR, Anderson J, Fugisang H. Effects of various concen- http://bjo.bmj.com/ and optic nerve were not seen in this study and could trations of diethylcarbamazine citrate applied as eye drops in not have been detected without fluorescein angio- ocular onchocerciasis, and the possibilities of improved therapy graphy. The transepidermal administration of DEC from continuous non-pulsed delivery. Br J Ophthalmol 1978; 62: as a 2% lotion was associated with a incidence 428-39. higher 8 Anderson J, Fuglsang H, Marshall TF. Effects of diethylcarb- of ocular changes than was the oral administration of amazine on ocular onchocerciasis. Tropenmed Parasitol 1976; 27: DEC. In particular, those patients receiving DEC 263-78. lotion had more microfilariae migrate into the 9 Garner A. Pathology of ocular onchocerciasis: human and anterior chamber and cornea. Patients experimental. Trans R Soc Trop Med Hyg 1976; 70: 374-7. on September 24, 2021 by guest. Protected copyright. receiving 10 Thylefors B, Brinkmann UK. The microfilarial load in the DEC lotion also had more new chorioretinal changes anterior segment of the eye. A parameter of intensity of develop during treatment. Of perhaps even greater onchocerciasis. Bull WHO 1977; 55: 731-7. significance was the fact that visual field constriction 11 Taylor HR, Langham ME, de Stahl EM, Figueroa LN, and optic nerve pallor occurred in patients in both Beltranena F. Chemotherapy of onchocerciasis: a controlled clinical trial of topical diethylcarbamazine (DEC) in Guatemala. groups. Tropenmed Parasitol 1980; 31: 357-64. In terms of safety and efficacy there seems to be no 12 Thylefors B, Tonjum AM. Visual field defects in onchocerciasis. reason to prefer DEC lotion to DEC tablets, since BrJ Ophthalmol 1978; 62: 462-7. previous reports have shown that DEC lotion is only 13 Bird AC, El-Sheikh H, Anderson J, Fuglsang H. Changes in visual function and in the posterior segment of the eye during marginally better than placebo lotion" and far less treatment of onchocerciasis with diethylcarbamazine citrate. BrJ effective than DEC tablets3 in reducing microfilarial Ophthalmol 1980; 64:191-200. skin-snip counts. DEC lotion also produces at least as 14 Thylefors B, Rolland A. The risk of optic atrophy following many systemic side effects as DEC tablets. Therefore, suramin treatment of ocular onchocerciasis. Bull WHO 1979; 57: 479-80. from the present study there seems to be no reason 15 Anderson J, Fuglsang H. Further studies on the treatment of for contemplating the use ofDEC lotion to reduce the ocular onchocerciasis with diethylcarbamazine and suramin. BrJ ocular involvement in patients with onchocerciasis on Ophthalmol 1978: 62: 450-7. the grounds that the lotion has less 'toxic' 16 Greene BM, Taylor HR, Humphrey RL. Proteinuria associated side effects, with diethylcarbamazine treatment of onchocerciasis. Lancet or that it protects the eye by encouraging or allowing 1980; i: 254-5. the microfilariae to migrate from the eye to other 17 Greene BM, Taylor HR, Humphrey RL, Lawley TJ. Circulating Br J Ophthalmol: first published as 10.1136/bjo.65.7.494 on 1 July 1981. Downloaded from

502 Hugh R. Taylor and Bruce M. Greene

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