Year : 1981 | Volume
: 29 | Issue : 4 | Page : 355--358
Penicillamine-A new therapy of retinitis pigmentosa
Dr. Rajendra Prasad Centre for Ophthalmic Sciences, New Delhi, India
D K Gahlot
Dr. Rajendra Prasad Centre for Ophthalmic Sciences, New Delhi-110029
|How to cite this article:|
Gahlot D K. Penicillamine-A new therapy of retinitis pigmentosa.Indian J Ophthalmol 1981;29:355-358
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Gahlot D K. Penicillamine-A new therapy of retinitis pigmentosa. Indian J Ophthalmol [serial online] 1981 [cited 2020 Sep 24 ];29:355-358
Available from: http://www.ijo.in/text.asp?1981/29/4/355/30930
Retinitis Pigmentosa is a genetically determined primary degenerative disorder of the retina. Its aetiology is unknown and treatment unsatisfactory. On the basis of our previous findings it was postulated that retinitis pigmentosa may be a condition of chronic copper toxicity due to inborn error of metabolism. The potentiality of copper to act as an extraneous toxin capable of inducing generative changes in the rabbit retina in many ways similar to human retinitis pigmentosa has also been shown. A clinicotherapeutic trial of penicillamine in these cases was, therefore, undertaken, the report of which is presented here.
MATERIALS AND METHODS
7 patients of retinitis pigmentosa, 5 males and 2 females between 8 and 50 years of age were taken. The diagnosis was confirmed by history, fundus picture and electrophysiological studies which included electroretinography and electro-oculography as reported earlier. The selection of cases was entirely based on the patient's willingness to undergo the trial and bear the expenses involved, the average cost of treatment being about Rs. 20 or £ 1 per day.
Systemic, general and neurological examination of all the patients revealed no abnormality. Routine blood and urine tests were negative. Biochemical tests with regards to copper metabolism were conducted as reported earlier.
In previous communication low copper oxidase activity was reported in all cases of retinitis pigmentosa Here cases V & VI have, however, shown normal copper oxidase activity indicating that this parameter may show some variation.
The patients were kept on a strict low copper diet. They were advised to drink distilled water or coca cola ad lib as local tap water was found to have high copper content. No condiments were allowed and table salt was replaced with analytic sodium chloride. All patients except case VI being vegetarians were instructed to take increased quantities of whole milk, curd milk products to maintain adequate protein intake. All the previous medicines were discontinued and the actual schedule of therapy was as follows:
i) Low copper diet containing about 1 mg copper daily.
ii) Potassium sulphide (40 mg) capsules with each meal.
iii) Penicillamine (Cupri mine- Merck, Sharp & Dohme) 250 mg. capsules 2 hours before each meal and 3 hours after dinner starting with 2 capsules a day and increasing gradually to 8 capsules a day.
iv) Pyridoxine tablet (Benadone-Roche) 20 mg a day.
During the course of therapy a close watch was kept on the allergic reactions on the skin and mucous membranes and a night temperature record was maintained for the first 4 months. The haematological state was monitored by the haemoglobin, total 8 differential and platelet count twice a week for the first 4 months; every week for 10 months and every fortnight for the rest of the period. 24 hour urine was estimated to monitor the copper excretion every week for the first 4 months and every 2-3 months for the rest of the period. Frequent urine check up for albumin and sugar were also done.
Perimetry was repeated under identical conditions. Visual fields being often irregular were measured according to their surface area in mm 2 with the help of a planimeter and converted into percentage figures taking normal field area as 100%. Nystagmoid movements were recorded by electronystagmography.
The follow up period in cases I & II was 24 months; case III, 22 months; case IV & V 12 months; case VI, 10 months & case VII, 6 months.
The results of treatment with penicillamine are shown in [Figure 1][Figure 2][Figure 3]. The parameters for assessment were visual acuity, visual fields, electroretinography, electrooculography, electronystagmography and audiometry. Visual fields have been expressed quantitatively in percentage figures.
The findings show that following penicillamine therapy irrespective of initial difference in biochemical parameters, visual acuity has improved in all [Figure 1], visual fields in three (Case II, V, VI) [Figure 2] and nystagmoid movements in all (Case I-IV) [Figure 3]. Electrophysiology has, however, shown no improvement so far. There is also no change in the fundus picture or lenticular opacities.
Audiometry in cases I to IV also improved, the details of which are reported elsewhere. Deafness in case VI did not improve.
Retinitis Pigmentosa is a degenerative disease of the retina characterised by chronic progressive course starting in about Ist decade of life as night blindness and leading to total blindness by 4th or 5th decade. Its aetiology is not known and various types of therapies have failed either to improve or arrest the condition.
Our new aetiological hypothesis that retinitis pigmentosa may be a condition of chronic copper toxicity was put to a therapeutic test by keeping these patients on oral penicillamine. Penicillamine is a bi-sulfide bond cleaving agent and a derivative of sulfhydryl aminoacid 3-mercaptoxaline. It has an special affinity to chelate copper and is an established form of therapy in Wilson's disease.
Penicillamine as a form of therapy in retinitis pigmentosa is not known.
An assessment of the effectivity of any treatment in retinitis pigmentosa is a difficult task since this disease is known to undergo periods of natural remmissions. However, these remissions are of small degree and last for relatively short periods. Following penicillamine therapy however, it is seen that not only no patient has deteriorated during the period of follow up, there is a progressive improvement in the visual status of these patients starting in as early as 1 month (Case II) and as late as 6 months (Case 1). The most significant observation is the persistence of visual acuity at the improved level during the entire period of follow up which extends to 2 years. This observation that the visual status of cases I-V has attained a stationary level for sometime may indicate that they may probably not improve any further, [Figure 1]. A similar finding is seen in visual fields [Figure 2]. It appears that the degree of visual improvement is essentially related to the retinal and macular damage already present.
The findings reported here are thus significant. On one hand they substantiate our previous suggestion that retinitis pigmentosa may be caused by a defect in copper metabolism and on the other they demonstrate that the visual damage occurring in this disease is to some extent reversible and that every patient howsoever 'blind' is worth a sincere trial. This may mean that the disease primarily has a functional component to which a structural component is added later and that reversibility is subject to the degree of structural changes present in the retina before beginning the treatment. The functional component may in some manner be related either to a functional block in retinal glycolysis or in rhodopsin cycle. The fact why electrophysiological parameters have not improved can only be commented after a larger series is analysed.
Seven proved patients of retinitis pigmentosa have been put on a trial therapy of penicillamine. It is seen that penicillamine is effective in producing clinical improvement both as regards visual acuity and visual fields.
|1||Adler, F.H., 1965, Physiology of the Eye ed. IV p. 580. The C.V. Mosby Co. St. Louis.|
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|4||Gaholt D.K., Sood V.P. and Khosla, P.K., 1977, J. Laryngol. Otol. 91:1107.|