|Year : 1961 | Volume
| Issue : 3 | Page : 51-55
A preliminary note on ocular manifestations in human ariboflavinosis
Narendra Swarup, SV Apte, MC Swaminathan
Institute of Ophthalmology, Nutrition Research Laboratories, Hydrabad, India
|Date of Web Publication||7-Apr-2008|
Institute of Ophthalmology, Nutrition Research Laboratories, Hydrabad
Source of Support: None, Conflict of Interest: None
|How to cite this article:|
Swarup N, Apte S V, Swaminathan M C. A preliminary note on ocular manifestations in human ariboflavinosis. Indian J Ophthalmol 1961;9:51-5
|How to cite this URL:|
Swarup N, Apte S V, Swaminathan M C. A preliminary note on ocular manifestations in human ariboflavinosis. Indian J Ophthalmol [serial online] 1961 [cited 2019 Mar 26];9:51-5. Available from: http://www.ijo.in/text.asp?1961/9/3/51/40273
It has long been recognised that ocular disturbances can occur in association with nutritional deficiencies. In the earlier period of the study of vitamin deficiency numerous investigators have referred to eye changes in rats deficient in riboflavin. Day Darby & Longstem (1937) reported multiple ocular effects due to riboflavin deficiency. Subsequently Bessey & Wolback (1939) called attention to vascularisation of the cornea as a specific and reliable criterion of riboflavin deficiency in the rat.
Sydenstricher et al (1940) Kruse et al (1940-41) described corneal vascularisation due to riboflavin deficiency in man. In spite of numerous reports which have appeared since this time considerable controversy still exists as to the specificity of ocular manifestation as an index of Ariboflavinosis in man. Stem (1950) in a critical review of corneal vascularisation in human ariboflavinosis had opined that : (a) corneal vascularity of riboflavin deficiency is quite specific and pathognomonic, (b) Limbal congestion and circumcorneal injection may appear in early deficiency stage but it is non-specific and non-pathognomonic for ariboflavinosis, (c) Lower tissue concentration of riboflavin for a period always leads to corneal vascularisation which may precipitate by chemical or mechanical trauma.
In contrast, Lyle et al (1944) are of the opinion that corneal vascularity is not necessarily due to dietary deficiency as it was observed that in cases of inadequate diets, it did not always improve when the deficiency was corrected. McGreary et al (1944) are of the view that corneal vascularity may indicate past riboflavin deficiency and it does not improve with therapeutic trials with riboflavin. Youmans et al (1942) have expressed that corneal vascularisation bears no relationship to dietary intake of riboflavin or deficiency of riboflavin. They claim that this ocular manifestation is more common in white subjects and does show variation with seasons. They also suggest that corneal vascularisation may be due to local riboflavin deficiency caused by local destruction of riboflavin, by visible or ultraviolet light. Scott's (1944) conclusions relating corneal vascularisation and racial differences are in agreement with Youman (locite).
In view of these varying and sometimes contradictory observations preliminary investigation was undertaken to study corneal vascularisation in human subjects manifesting other clinical signs of aribo-flavinosis.
| Material & Methods|| |
Twenty seven subjects were investigated and followed up during the period of treatment. These included 10 adults and 17 children. Nine of the adults were females and 1 male, among children there were 10 boys and 7 girls. Those subjects who did not show any clinical manifestations were included, to study normal slit lamp observations.
(1) All subjects were initially examined for clinical manifestation of B. complex deficiencies pertaining to oral cavity and tongue. They were then examined at Sarojini Devi Hospital with slit lamp microscope for evidence of vascularisation of cornea and other changes in the eye.
(2) Therapeutic trials were carried out with (a) Vitamin B complex tablets with the following composition:
i) Thiamine Mononitrate 10 mgm.
ii) Riboflavin. 3 mgm
iii) Nicotinic acid 15 mgm
iv) Pyridoxine Hydrochloride 2 mgm
v) Calcium Pantothenate 3 mgm
(b) Riboflavin and (c) Nicotinic acid.
The cases were divided into 3 groups. The 1st group consisting of 10 cases was given 2 tablets of B complex per day.
The 2nd group of 8 cases was given 2 tablets of Riboflavin per day (5 mgm/tab).
The 3rd group of 7 cases received Nicotinic acid amide2 tablets of Niacin per day (50 mg tablet.)
(3) The progress of the clinical condition and slit lamp microscopy were recorded at frequent intervals.
Clinical Picture : It was observed that 13 out of 25 cases showed combined lesions of angles of mouth and tongue and other 12 only lesions of the angles of the mouth.
(2) More than 22 subjects could be grouped into mild and moderate degrees of lesions of angle of mouth (and only 3 into severe degree of lesions of angle of mouth).
(3) Lesions of tongue had equal distribution in the following three groups :-
a) Only tips of tongue-red
b) Tongues-Glazed and fissured.
c) Glossitis- red raw tongue.
(4) Corneal Vascularization.
The vascularisation which was seen in most of the cases was limited to sectors, commonly in down and out, up and out, up and in or down and in position. The conjunctival vessel was thickened and engorged, bifurcating and running parallel to limbus.
Results : (1) From the results of therapeutic trials it has been observed that lesions of angles of mouth and tongue were not specific to any particular Vitamin B complex component.
(2) The progress of different cases varied considerably.
(3) In the group receiving multi Vitamin B, 9 cases out of 10 showed complete healing, while two cases out of 9 were quite irregular in their attendance. One case which did not show complete healing had frequent recurrences of the lesions. (Case No. 3 described).
(4) In the Riboflavin treated group out of 8 cases, only five subjects showed complete healing while in the other three cases there were mild signs of angular stomatitis.
(5) In the Niacin treated group only 2 subjects out of 7 showed complete healing while in others angular stomatitis deteriorated.
Results of the Slit Lamp Microscopy : In the B complex treated group two subjects showed vascular arcades initially and after the treatment. Four more subjects developed corneal extension of previous vascularisation which was limited upto limbus. All these subjects showed improvement in oral lesions. (One case showed recurrent exacerbation of angular stomatitis together with appearance of arcades).
In the Riboflavin treated group initially four cases had corneal vascularisation while after treatment only two showed corneal vascularisation. Case No. 18 described had corneal vascularisation which progressed in the initial stages and later showed regressive changes.
In the Niacin treated group, 3 out of 7 subjects had initial corneal vascularisation which showed regressive changes. At the end of the investigations, 2 cases who previously did not show corneal vascularisation did develop corneal vascularity. Three cases which initially did not show corneal vascularisation, developed corneal vascularisation which regressed progressively and at the final stages cornea did not show any arcades.
The conjunctiva was raised over these thick branches. From these vessels tiny twigs run towards cornea and formed loops. These vessels which entered the cornea either as arcades or as twigs were so fine that a single R.B.C. could pass in their lumen. In none of the cases the vascularisation was found all round the limbus and in only 14 eyes in 28 patients, vessels were found entering the cornea within limbus before treatment was started. In another 8 eyes vascularisation was present in conjunctiva only i.e. it was outside the limbus. The various observers have claimed that the characteristic vascularisation of ariboflavinosis is the one which is present all round the limbus with definite entry into the corneal substance. Some observers e.g. Lyle have contradicted this and have claimed that the vascularisation can be patchy as has been observed in this series of cases.
One would expect that vascularisation is present in both eyes as it is a response to dietary insufficiency, but in this series eight eyes out of 14 eyes showed uniocular affection.
The earliest change observed on slit lamp was marked. proliferation and engorgement of limbal plexus with very narrow capillary loops which outline extreme margin of scleral digitations and obliterate the narrow vascular zone between the limbal plexus and the sclero-corneal junction.
This progressed to vascularisation of cornea, if not treated and regressed if treatment was instituted. The capillaries lie just below the epithelium and anastamose to form row of loops from which new capillaries arise. This progress of anastamosis of capillaries continues until an extensive vascularisation is produced.
Later vessels grow in various depths of substantia propria with deep vessels in cornea like I.K None of the cases in this series showed this type of lesion.
Superficial and interstitial opacities also develop sooner or later. In this series no case showed opacities in cornea either superficial or deep.
It is observed that the vascularisation continued to progress or developed, after treating definite cases of ariboflavinosis with Vitamin B complex tablets containing 7 mgm of Riboflavin per day, while when treated by Riboflavin 10 mgm. per day alone there was a good response in four cases out of seven. One case did not come for followup, while one case developed new vascularisation.
In the Niacin group the observations are bizarre as the 4 cases which were showing vascularisation before treatment did not show any vascularisation afterwards. On the other hand 4 eyes which did not show vascularisation before, developed. new vascularisation after treatment.
| Other Findings|| |
(1) Out of 27 subjects examined for slit lamp microscopy 18 showed a pigmentary rim around limbus. Rao, et al (1940), Dhurandhar and Boman Behram (1940).
(2) Out of 27 cases, clinically only 3 subjects showed Bitot spot and dryness of conjunctiva on slit lamp examination, 6 more subjects showed Xerotic patches.
Case No. 3: A. Y. male 6 Yrs. Initial examination showed that child had mild angular stomatitis and without involvement of margin, Slit lamp microscopy showed only pigmentary rim at limbus but no vascularisation. He was put on Vit. B complex tablets 2/day. After 3 to 4 weeks stomatitis remained same but in both eyes there were development of vascularisation around limbus. Cornea was definitely not involved. After another interval of 4 to 6 weeks, child showed that his angular stomatitis was progressive, but there was no vascularisation. of cornea which was limited upto limbus as before. Later examination showed that angular stomatitis had slightly improved and the vascularisation at limbus in left eye had regressed considerably while in right eye it was same as before. All through the period the child was under treatment with Vitamin B complex.
Case No. 18: S. Male 9 Yrs. Initial examination showed clinically mild angular stomatitis, ulcerations of the lips and glazed tongue. The slit lamp examination showed that in both eyes there were pigment bundles around the limbus. Twigs of vessels bifurcating and running concentric to limbus, from where few tiny capillaries one cell thick were seen entering cornea at few spots specially upper and inner portion in the right eye and upper and outer portion in the left eye. The child was given 2 riboflavin tablets a day. Second examination after 4 weeks interval showed that angular stomatitis had completely healed while tongue was quite normal. Slit lamp examination showed clear cornea but presence of vascularisation around limbus.
Case No . 14: O Male 7 Yrs. Showed : (1) Mild angular stomatitis more marked on left side, (2) Lip and margin of the tongue were red and raw, (3) Lower lip showed hypopigmentation, (4) Conjunctiva showed Xerosis but no bitot spots. Subjectively he complained of burning of tongue while taking food. Slit lamp microscopy revealed that there was pigment around cornea and both eyes showed arcades in the cornea especially right eye in lower and outer quadrant, while left eye in upper and outer side. Child was treated with Riboflavin tablets 2i day. Second examination revealed that clinically there was progressing angular stomatitis alter initial regressive changes in the oral signs. Slit lamp microscopy showed regression of vascularisation of cornea in both eyes, but in right eye there were few vessels around the limbus.
Case No. 22: L. Female 10 Yrs. Showed : (1) Mild angular stornatitis and redness of the tip of the tongue. There were no subjective symptoms. Initially slit lamp examination showed no abnormal changes in the eye; especially around the limbus and cornea. The child was given 2 Niacin tablets a day. As the case was followed up the angular stomatitis was progressive while tongue definitely showed signs of glossitis. Second examination by slit lamp showed definite development of vascularisation around limbus as well as in the cornea in both eyes. These changes when observed again showed progressive trend but in the left eye it was suggestive of Trachomatous panus. 3-4 weeks after the second examination, clinical signs were still progressing, while slit lamp examination showed vascularisation around the limbus from where few vessels were entering in the cornea of right eye in the inner and lower as well outer part but in left eve cornea was free of vessels. Further examination revealed same clinical picture but slit lamp definitely showed complete clarity of the cornea in both eyes while vessels were still seen around limbus.
Case No. 20: F 45 Yrs. Complained of tingling and numbness of whole body involving scalp, and burning of the tongue on washing. Clinically she showed presence of mild angular stomatitis with normal tongue. Slit lamp revealed : (1) Mild pigment in lower part of the limbus; (2) No arcades and vascularisation in left eye. (3) In right eye there was pterygium on the inner side of the cornea and arcades in the upper part. She was given 2 Niacin tablets a day. Examination after 2 weeks showed moderate angular stomatitis, fissured glazed round type. Slit lamp microscopy showed (1) in left eye circum-corneal congestion and presence of pannus, (2) in right eye persistence of arcades. Examination after another 4 weeks interval showed same clinical signs while slit lamp showed (1) in the right eye development of 2-3 arcades in the outer and lower part while (2) in left eye there were no arcades but pannus was present. Last examination after another interval of 4 weeks showed clinically same condition while slit lamp showed regression of arcades in left eye but presence of pannus in both eyes.
| Summary|| |
Ocular manifestation in human ariboflavinosis are studied with a view to elicit effect of therapeutic trials with different Vit. B-complex components.
In 27 patients with clinical manifestations of the oral and ocular lesions the response to treatment is described.
The probable pathogenesis of corneal vascularisation is discussed.
| Acknowledgements|| |
Authors wish to convey their grateful thanks to Dr. V. N. Patwardhan former Director, Nutrition Research Labs, Dr. C. Gopalan, the present Director, Dr. P. Ramchander, Superintendent Sarojini Devi Hospital, Dr. K. Someshwar Rao, Dy. Director, Indian Council of Medical Research, for their keen interest and guidance during the investigations and study.
| References|| |
Ressey, O, A, and Wolbach, S.B., J. Exp. Aled., 1939, 69, page 1,
Day, P. L.; Darby, W.J. and Longstem, W.C., J. Nutri. (1937), 13, 289.
Dhurundhar, C. B. and Roman Rehram A. K.. Ind. jour. Med. Res. 1940, 27, 35
Kruse, H. D., Sydenstricher, V. P., Sehrell, W. H., and Cleckley, H. H.; Pub. Health Rep. Washington, 1940, 55, P. 157.
Lyle, T. K., Macrere, T. F. and Gardiner, P. A.; Lancet, 1944, 246, 393.
MacGreary, J. F. Nicholls, V. V. and Tisdall, F. F.; Canad. Med. Assn. J. 1944, 51, 106.
Rao, K.S., Menon, P. S. and De N. K., Ind. Jour. Med. Res. 1951, 39, 583.
Scotts, J. G., Jour. Roy. Amm. Med. Corps. 1944, 82, 133.
Stern, J. J., Ame Jorn. Ophthalmo1. 1948, 33, 1127.
Sydenstricher, V. P., Sebrell, W. H., Clecklay, H. M. and Kruse, H. D.; J. Ame. Med. Assoc., 1940, 114, 2437.
Youmans, J. B., Patton, E. W. Robinson, W.D., and Kern, R.; 1942. Trans. Assoc. Amer. Phys., 57, 6.