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Year : 1961  |  Volume : 9  |  Issue : 3  |  Page : 51-55

A preliminary note on ocular manifestations in human ariboflavinosis

Institute of Ophthalmology, Nutrition Research Laboratories, Hydrabad, India

Date of Web Publication7-Apr-2008

Correspondence Address:
Narendra Swarup
Institute of Ophthalmology, Nutrition Research Laboratories, Hydrabad
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Source of Support: None, Conflict of Interest: None

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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 2021 Dec 8];9:51-5. Available from: https://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 Top

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 Top

(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 Top

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.[11]

  Acknowledgements Top

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 Top

Ressey, O, A, and Wolbach, S.B., J. Exp. Aled., 1939, 69, page 1,  Back to cited text no. 1
Day, P. L.; Darby, W.J. and Long­stem, W.C., J. Nutri. (1937), 13, 289.  Back to cited text no. 2
Dhurundhar, C. B. and Roman Rehram A. K.. Ind. jour. Med. Res. 1940, 27, 35­  Back to cited text no. 3
Kruse, H. D., Sydenstricher, V. P., Sehrell, W. H., and Cleckley, H. H.; Pub. Health Rep. Washington, 1940, 55, P. 157.  Back to cited text no. 4
Lyle, T. K., Macrere, T. F. and Gardiner, P. A.; Lancet, 1944, 246, 393.  Back to cited text no. 5
MacGreary, J. F. Nicholls, V. V. and Tisdall, F. F.; Canad. Med. Assn. J. 1944, 51, 106.  Back to cited text no. 6
Rao, K.S., Menon, P. S. and De N. K., Ind. Jour. Med. Res. 1951, 39, 583.  Back to cited text no. 7
Scotts, J. G., Jour. Roy. Amm. Med. Corps. 1944, 82, 133.  Back to cited text no. 8
Stern, J. J., Ame Jorn. Ophthalmo1. 1948, 33, 1127.  Back to cited text no. 9
Sydenstricher, V. P., Sebrell, W. H., Clecklay, H. M. and Kruse, H. D.; J. Ame. Med. Assoc., 1940, 114, 2437.  Back to cited text no. 10
Youmans, J. B., Patton, E. W. Robinson, W.D., and Kern, R.; 1942. Trans. Assoc. Amer. Phys., 57, 6.  Back to cited text no. 11


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