On the ocular findings in ochronosis: a systematic review of literature

Abstract

Background: Ochronosis/Alkaptonuria is a tyrosine metabolism disorder where accumulation of homogentisic acid, in eye, skin, cartilage and several other connective tissues leads to a black pigmentation of the affected tissues. It is autosomal-recessive inherited in men with a frequency of 1-9/1,000,000. While it is clear that pigment deposits lead to joint destruction, renal stone formation and cardiac valvulopathy respectively, the significance of ocular findings is still unclear. We therefore aim to evaluate the frequency and clinical significance of ocular findings in ochronosis and discuss possible therapeutic options.

Methods: Systematic review of literature via Medline and Web of Science. Only case reports in English, German, French, Spanish or Italian documenting detailed ophthalmologic examination were included.

Results: Our search revealed 36 case reports including 40 patients. Average age at the onset of ocular signs was 40.6 years. The most frequent sign was symmetric brown sclera pigmentation present in 82.5 percent of the patients. "Oil-drops", brown pigment spots in the limbus are generally considered pathognomonic but were a little less frequent (75 percent). Vermiform pigment deposits at the level of the conjunctiva or increased conjunctival vessel diameter is also frequent. We found an increased incidence of central vein occlusion and elevated intraocular pressure going along with chamber angle hyperpigmentation. Another condition observed twice is rapid progressive astigmatism attributable to corneoscleral pigment accumulation.

Conclusion: Our observations suggest that ocular findings are of double relevance. First, characteristic ocular findings can anticipate the time of diagnosis and second, ocular findings may complicate to various conditions putting sight at risk. Opthalmologists and general physicians should be aware of both. Therapeutic options include protein restriction, administration of high dose vitamin C or nitisonone. Evidence for all of them is limited.

Figure 1

Tyrosine metabolism pathway in health (black) and AKU (ochre) [10],[11]. Metabolites are drawn in Boxes, enzymes are given in bold. Red: Defect in AKU. Blue: Sites of possible therapeutic interventions.

Figure 2

Biomicroscopic findings in ochronotic eyes. Left: Symmetric brown scleral pigmentation at 3 and 9 o’clock (w. permission [31]). Middle: “Vermiform” pigment accumulation in the conjunctiva (Courtesy of Dr. U. Hackethal [88]). Right: “Oil drops” of the corneal limbus (w. permission [31]). All images show the right eye.

Figure 3

Histopahtologic slice through a specimen obtained from the conjunctiva (Hematoxilin-Eosin staining). P: Ochronotic pigment, E: Conjunctival epithelium, SP: Substantia propria, G: conjunctival vessel. Courtesy of Dr. U. Hackethal [88].