|Year : 1989 | Volume
| Issue : 3 | Page : 118-120
Methodology for studies on medical therapy of cataracts : cataract II
YR Sharma, RB Vajpayee, R Bhatnagar, Madan Mohan, RV Azad, Mukesh Kumar, Ram Nath
Dr. R.P. Centre for ophthalmic Sciences, A.I.I.M.S, Ansari Nagar, New Delhi- 110 029, India
Y R Sharma
Dr. R.P. Centre for ophthalmic Sciences, A.I.I.M.S, Ansari Nagar, New Delhi- 110 029
Source of Support: None, Conflict of Interest: None
The methodology for testing any possible effect of potential anti-cataract agents is described. This is based on slit lamp and ophthalmoscopic cataract classification and on visual acuity. The difficulties encountered in such studies are highlighted. The presented methodology is suggested to be fairly adequate in assessing usefulness of any possible medical therapy of cataracts.
Keywords: Lens classification; Medical therapy of cataracts; Aspirin; Glutathione; Sulindac; Vitamin E
|How to cite this article:
Sharma Y R, Vajpayee R B, Bhatnagar R, Mohan M, Azad R V, Kumar M, Nath R. Methodology for studies on medical therapy of cataracts : cataract II. Indian J Ophthalmol 1989;37:118-20
Medical therapy of cataracts remains a controversial subject. In many countries topical or systemic medications are marketed which claim to slow down or stop the progress of cataracts , Retrospective data has been used to suggest clinical efficacy of aspirin in slowing down the progression of cataract in senile non-diabetic and diabetic cataracts ,,,. Prospective studies evaluating the medical therapy of cataracts are available but in general the follow up is limited ,. One long term (two years) follow up study using Catalin was found to be ineffective . Well planned studies have been reported but the rationale of choice of the screened drugs remains unclear . It has been suggested that studies on medical therapy on cataracts are a long term proposition  and that proving the efficacy of any therapy for adult cataracts may be all but impossible . It has been stated that valid proof could require thousands of patients using a treatment for a minimum of 5 to 10 years .
Lacking an exact photographic documentation system, we devised a system of clinical lens classification based on slit lamp and direct ophthalmoscopic examination  The inter and intraobserver variability using our classification scheme was found to be fair to excellent. We adopted this classification in studying the efficacy of systemic Aspirin and systemic Vitamin E, topical glutathione drops in slowing down the progress of cataract. Guidelines for such studies have been described . Reported herein is the methodology we adopted. We will subsequently report the results obtained with the use of Glutathione topical drops, Sulindac topical drops and systemic Aspirin and Vitamin E using the methodology described herein.
| Material and methods
The studies were conducted on hospital based patients. Patients 38 years and above attending the general out patient department were referred to the central cataract cell. After a brief ophthalmic and systemic history, best corrected vision was recorded and anterior segment slit lamp examination was done. Pupils were maximally dilated using Homatropine 2 percent eye drops and 10 percent phenylephrine eye drops. After maximal pupillary dilatation, the lens was studied using slit lamp and direct ophthalmoscope. The lens was classified as normal or if any lens opacity was present, it was classified and graded on a separate printed proforma based on our classification system sub . Patients whose pupils did not dilate or in whom pupillary dilatation was contra indicted, were excluded from the study. Also excluded were those who had any eye pathology which could be linked to the occurrence of cataracts. Patients having greater than + 4 diopter of refractive error were also excluded. A prerequisite for inclusion into the study was normal posterior pole and normal optic disc examination. These data were recorded for all patients referred to the cataract cell. Based on the examination, the patient was classified as having cataractous or normal lens. Patients were classified as normal when no lens capacity was present, the best corrected vision was 6/6 and when the presenting complaint and findings thereof lacked any known correlation to occurrence of senile cataracts. An exception here was presence of diabetes and hypertension. If retinopathy was absent in patients of diabetes and hypertension, they were entered randomly in the appropriate study as control and cataract patients. Senile cataract was diagnosed irrespective of visual acuity when lens opacity was present and no condition existed which could be linked to occurrence of senile cataracts except diabetes and hypertension. For medical therapy of cataract, only patients having vision of 6/60 or better were included in this study.
It was important to determine if the patients could come for regular monthly follow up. In all patients who could come for regular follow up written informed consent was obtained. Consecutive senile cataract patients with known history of diabetes who were referred to the cataract cell and who met the above criteria were put on topical sulindac 1 percent eye drops with placebo treated eye serving as control. For topical glutathione studies, similarly, patients having senile cataract with no known history or evidence of diabetes were put on glutathione drops in the eye with the more advanced cataract and placebo vehicle drops in the fellow eye. For systemic cataract studies, patients were randomly allotted to control group who received 1 tablet tid of Aspirin tablet excipients, aspirin group which received one 325 mg tablet of aspirin tid and Vitamin E group which received one 400 mg. capsule daily. We were unable to get placebo tablets which were similar to Vitamin E capsules - so the strategy of controls receiving three aspirin tablet excipients daily had to be adopted. The placebo group was control for both the aspirin and the Vitamin E treated groups. Due to various constraints of manpower and others, a double blind approach could not be adopted. It was decided to follow up patients at monthly intervals. This was necessary to replenish their medication supply but if a patient belonged to a distant place and wished to be included in the study, sufficient medications with proper instructions were supplied to enable him to come every three months for follow up.
A minimum follow up of two years was planned. Patients were examined at monthly intervals (a few at three month intervals). At each follow up, the examination procedure was repeated and data recorded on a separate study sheet. To obviate (lessen), bias previous data was not referred to . This record was attached to the patient's coded sheet at each follow-up. At each follow up special care was taken to enquire into any possible undesirable side effects. These studies were carried out between January 1985 and October 1987.
| Comments on methodology
First of all, the studies were not double blind. We recognise this major pitfall but feel that because at each follow up previous records were not referred to, the bias is lessened. Secondly, our classification system permits a very detailed objective record which included a number of parameters. Thirdly, we certainly do not feel that our studies are at all conclusive. We only submit that with the methodology adopted, it may be possible to identify the potential drugs which can be further tested in large double blind studies, if possible, with additional photodocumentation. Lastly, it is felt that reporting our methodology and our experience with studies on medical therapy of cataract, highlights some of the difficulties that others engaged in such studies are likely to encounter. For all groups, the following relevant data was recorded. Age, sex, best corrected vision, percentage visual loss calculated according to the chart of Sterling and Snell , cortical opacity extent and density, nuclear opacity extent and density, PSC capacity extent and density (determined by slit lamp) and ophthalmoscopically graded opacity extent and density. Any patient whose vision dropped to 3/60 or less was not followed up further in the study. At the conclusion of the study, these data were tabulated for each of the three groups i.e. Sulindac group, Glutathione group and systemic group of control patients, patients on Aspirin and patients on Vitamin E. Several difficulties arise here. The exact numbers and data will be reported separately with the individual group. The primary difficulty was that there were very few patients in each group who completed the 2 years follow up. Various factors could have contributed to this. Indeed very few patients did complete the one year follow up. To have a significant number of patients in the three groups any patient who had completed three months follow up was included for data analysis. Thus follow up ranged from 3 months to 24 months. For all patients thus analysed in each group loss of vision was calculated as same vision, loss of upto 2 lines, loss of upto 4 lines, loss of upto 6 lines and loss of upto 8 lines or more. The number of such eyes is subjected to analysis in each group. The percentage visual loss during the follow up is computed for each patient and an average arrived at by adding this percentage for the whole group and arriving at a mean loss with standard deviation. This was felt to give an overall impression of the loss of vision in a group as a whole. The same methodology was used in separately calculating extent and density of slit lamp classified cortical, nuclear, PSC cataracts and ophthalmoscopically classified extent and density of opacity. Using this methodology a mean is arrived at by adding the opacity present in all eyes and dividing by the number of eyes in that group. An eye not having a particular opacity is given a percentage score of 0. For instance, if a group had 40 eyes, 20 may not have cortical opacities and so each of these is assigned zero percentage. The mean is arrived at by adding cortical opacity extent present in remaining 20 eyes divided by the number of eyes i.e 40.
The standard deviation calculated using this approach almost nears mean, but statistically is acceptable , For each type of opacity in a group as a whole the progression of extent of opacity or density graded on a . scale of 0 to 3 + is available as one figure which can be compared statistically with the control group. For each type of opacity the actual number of eyes having that opacity is computed separately.
Whenever possible an attempt is made to analyse pure cataracts and mixed cataracts separately. But again preponderance of mixed cataracts was so heavy in each group that the number of pure cataract patients in any group was seldom sufficient for statistical analysis. Furthermore, many cataracts which start as pure types ultimately end up as mixed types.
The methodology described herein for medical therapy of cataracts test a number of parameters. These parameters which include visual acuity loss and extent and density of lens opacities classified anatomically should permit a fair assessment of potential anti-cataract drugs which can be further screened in large double blind studies preferably with photodocumentation. Such studies entail expensive equipment, a complex set up and involve great manpower ,. Studies using anticataract agents have been reported with 3 months follow up which actually reported reversal of lens opacity ,. These studies were based primarily on actual vision improvement. Such studies have been criticised and often ridiculed .
Our experience with medical therapy of cataracts highlights several difficulties. A very large drop out rate is possibly explained by the patient learning that cataract can be surgically cured, comment by other ophthalmologists about futility of such a study, suggestion that patient is actually being used as a guinea pig, patient suspecting the :votive for the free supply of medications, the cataract in lesser degrees often does not inconveniences the patient too much and other financial, time and unknown considerations. The high drop out rate highlights the difficulties likely to be encountered in any such long term prospective studies. Due to various constraints we could not make the studies double blind though we exerted caution of obviating bias by not referring to previous patient records. But double blind approach should certainly be adopted whenever practical. It is felt that the methodology described would suffice to fairly assess the potential of anticataract medications or other means in a set-up where manpower, financial and other constraints make it difficult to design large double blind studies with photographic documentation. For definite conclusions, large double blind multicentric photo-documented studies are essential.
Another problem is that cataracts can be of pure type or of mixed type. A potential drug may possibly affect one subtype of opacity and not the other. This would call for preselecting particular subtypes of cataract opacities. Gathering such pure subtypes alone would be difficult. Even if such subgroups are available, the problem remains that during follow up, pure cataract subtypes may change to mixed type by development of additional subtypes of opacities. The difficulties include what actually a potential anticataract drug is supposed to accomplish. Is it the preservation of vision, reduce the speed of (or visual loss) or is the effect on extent (or the density) of opacity more important-both often do not correlate. We treated cataract as one single entity and no attempt was made to match anatomical subtypes. Data analysis indicated that in our medical therapy studies, there were very few pure cataracts; mixed cataracts were overwhelmingly more common. The studies on effectiveness of medical therapy in mixed type of cataracts pose additional problems. The sub-types of opacities, their extent and density and their distribution may vary in control and treated eyes. In a mixed cataract, it is often difficult to decide which sub-type of opacity is more important and hence assessing potential usefulness of any medical therapy of cataract must address a number of parameters. It is for these reasons that we undertook to study various different parameters separately and analysed them independently of each other.
We thank ICMR India for partly supporting this study. Dr. Y.R. Sharma was appointed under the supernumerary research cadre scheme at Dr. R.P. Centre. We sincerely thank all residents who referred their patients to the cataract cell.
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