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   Table of Contents      
Year : 2019  |  Volume : 67  |  Issue : 10  |  Page : 1765-1768

Ocular manifestations in patient with congenital erythropoietic porphyria

Department of Ophthalmology, Miguel Servet University Hospital; GIMSO Research and Innovative Group, Aragon Institute for Health Research (IIS Aragón), University of Zaragoza, Zaragoza, Spain

Date of Submission25-Oct-2018
Date of Acceptance08-May-2019
Date of Web Publication23-Sep-2019

Correspondence Address:
Prof. C Isanta-Otal
GIMSO Research and Innovative Group, Aragon Institute for Health Research (IIS Aragón), University of Zaragoza, Zaragoza
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/ijo.IJO_1776_18

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We present the case of a 52-year-old woman referred to our service because of extreme ocular surface dryness. The patient showed corneal, conjunctival, and eyelid manifestations of ocular congenital erythropoietic porphyria (CEP). We started treatment with autologous serum, topical steroids, and cyclosporine twice a day, topical retinoids, and intense corneal lubrication. The patient referred significant improvement of ocular bothering and less discomfort since treatment was initiated. We describe the management of the herewith presented case of ocular CEP.

Keywords: Autologous serum, cornea, congenital erythropoietic porphyria, cyclosporine, retinoids

How to cite this article:
Isanta-Otal C, López-Valverde G, Orobia A J, Pablo L E. Ocular manifestations in patient with congenital erythropoietic porphyria. Indian J Ophthalmol 2019;67:1765-8

How to cite this URL:
Isanta-Otal C, López-Valverde G, Orobia A J, Pablo L E. Ocular manifestations in patient with congenital erythropoietic porphyria. Indian J Ophthalmol [serial online] 2019 [cited 2021 Mar 8];67:1765-8. Available from: https://www.ijo.in/text.asp?2019/67/10/1765/267400

Porphyrias are a rare metabolic disorder characterized by the deficiency of any of the enzymes required for the biosynthesis of the heme group, which leads to a collection of photosensitive toxic heme intermediates, called porphyrins, in various tissues of the body. Patients with this metabolic disorder may present either neurological or cutaneous symptoms. Congenital erythropoietic porphyria (CEP) is characterized with photosensitive skin lesions at areas exposed to sunlight. There are few case reports illustrating porphyria-related complications like cicatricial ectropion, pterygium, punctual stenosis, scleral and corneal thinning, and corneal perforation.[1],[2] However, sight-threatening complications, like keratolysis, leading to total corneal melt in the presence of other risk factors have rarely been reported.[3],[4],[5] We report a case of a woman diagnosed with CEP, presenting a serious variant of ocular disease.

  Case Report Top

A 52-year-old Caucasian woman diagnosed with CEP [based on raised red blood cell coproporphyrin (12.8 μg/100 mL) (normal range 0–1 μg/100 mL), raised urinary uroporphyrin (9000 μg/L), and raised fecal coproporphyrin (201 μg/g dry weight and relied on homozygous mutation in the uroporphyrinogen III consynthase gene], epilepsy, hypertension, hyperuricemia, and glaucoma on antiglaucoma medication (Timolol 2/day) was referred to our service to assess the performance of a keratoplasty. As systemic symptoms, she showed intense dermatological lesions on the face and extremities [Figure 1]. The patient is double homozygous for CEP. She had been followed in another center because of central corneal conjunctivalization of the right eye (OD) and the onset of inferior conjunctivalization of the left eye (OS). She complained of foreign body sensation, burning, and dryness, accompanied by progressive visual acuity loss in both eyes (OU). She had only been treated with artificial tears and lubricant ointments and eyelid hygiene.
Figure 1: Intense dermatological lesions on face (a) and extremities. Systemic features suggestive of resorption of distal phalanges noted in both upper extremities (b)

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Exploration revealed a visual acuity of 0.16 OD and 0.4 OS. Intraocular pressure in OU was 1 6mm Hg. On slit-lamp examination, the patient presented tear break-up time (TBUT) inferior to 1 second, central corneal pannus in OD, and lower epithelial irregularity with less severe conjunctivalization in OS [Figure 2]; associated with scales and keratinization of the eyelid margin and complete atrophy of  Meibomian gland More Detailss [Figure 3]. Schirmer test value without topical anesthesia was 3 mm in OD and 15 mm in OS. Fluorescein staining was positive with moderate affectation (grade III) in the Oxford Squeme.
Figure 2: Central pannus in OD (a) and severe conjunctivalization in OS (b)

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Figure 3: Meibography of both eyes where we can see complete atrophy of Meibomian glands. Right eye; upper eyelid (a) and lower eyelid (c). Left eye; upper eyelid (b) and lower eyelid (d)

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We suggested adding medical treatment with autologous serum 6 times a day or more as needed, cyclosporine 0.05% twice a day, topical steroids, and an ointment with vitamin A without preservatives and with anti-ultraviolet A radiation filter. After 4 months of treatment, the patient reported less eye discomfort and bothering with the only remaining signs being conjunctival hyperemia and corneal conjunctivalization [Figure 4] and [Figure 5]. Foreign body sensation and ocular discomfort have decreased and the progress of ocular involvement seems to have slowed down, TBUT persists up to 3 seconds, and fluorescein staining has decreased to minimal (grade I) in the Oxford Squeme.
Figure 4: Right eye follow-up. The only remaining signs of conjunctival hyperemia and corneal conjunctivalization in both eyes. Without staining (a) and with fluorescein (b), where no fluorescein-positive staining is seen

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Figure 5: Left eye follow-up. Without staining (a) and with fluorescein (b), where mild superficial keratitis can be seen

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After considering the possibility of performing a keratoplasty, we decided to wait longer until a better state of the ocular surface is achieved. To get more guarantees of avoiding graft rejection, we have proposed treating before corneal neovascularization (with fine needle cauterization). When possible, we will try a deep anterior lamellar keratoplasty (DALK), covering with amniotic membrane and lateral permanent tarsorrhaphy.

  Discussion Top

CEP usually presents with dermatological features including bullae, hyperpigmentation, scarring, pseudoscleroderma, and hypertrichosis in sun-exposed areas. [Table 1] summarizes the systemic manifestations of the disease after the review of the literature. The differences with other diseases that can be confused with CEP are shown in [Table 2]. The most common ocular involvement is painless, non-inflammatory scleral lesions in the interpalpebral areas.[6] The diagnosis of CEP is genetic. The exact mechanism of scleral damage in porphyria is still unclear. Takamura et al. found that the levels of porphyrins were raised in teardrops of patients with porphyria, suggesting excretion of heme precursors in tears, and suggested that sunlight triggers inflammation by activating porphyrins present in tears.[7] Hence, a combination of accumulated toxic metabolites in scleral end vessels with increased tear porphyrin levels predisposes sclera to necrosis and melting. However, the cornea is spared as it receives its blood supply from the limbal arcade, which is not exposed to sunlight.[8] Very few cases of corneal involvement have been reported in literature.[3],[4],[5]
Table 1: Review of the literature about systemic manifestations of the disease

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Table 2: Congenital Erythropoietic Porphyria differences with other similar diseases

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As described by Arya et al.,[9] the limitation of this case study was that we were not able to collect any direct histopathological or biochemical evidence of the presence of porphyria in either the eyes or the tear film because the patient did not consent for a scleral or a conjunctival biopsy and we did not have the facility to process the tear film. However, we took indirect evidence from the typical clinical presentations in previously reported cases and tear studies to establish our diagnosis.[3],[4],[5],[8],[10] Such atypical presentations of CEP can mimic other inflammatory causes of scleritis, thereby demanding careful history taking and examination. It must be understood that unlike conventional thinking, these patients may progress to corneal perforation, especially in the presence of other risk factors. Therefore, in the presence of the progression of the disease, other risk factors should be evaluated.

Management depends upon the stage of CEP presentation. If the patient is at an early stage of the disorder, it is better to instill copious lubricant along with general protective measures. Vitamin A used topically and orally has been reported to speed epithelial healing. Vitamin A exerts a moderate antioxidant activity; it plays an essential part in epithelial growth and limbal stem cell differentiation, promoting corneal wound healing. Studies suggest that vitamin A may modulate the expression of thrombospondin-1 in the corneas to accelerate the re-epithelialization of wounded corneas. Scleral patch graft is mandatory to restore globe integrity. Considering the poor fate of grafts, Boston keratoprosthesis has emerged as a viable option, though a long-term follow-up is required. What actually triggers these recurrences is yet to be explored. We suggest long-term genetic studies to better understand the long-term history of the disease. Further studies regarding the care of patients with porphyrias are required to treat these rare ophthalmic conditions more effectively.

In conclusion, corneal involvement in CEP is a rare ocular manifestation with very complex therapeutical management. Lubrication is the main treatment, but in severe cases, it must be completed with autologous serum or topical retinoid in order to improve corneal conjunctivalization.

We must inform these patients that treatment is only symptomatic as there is no cure for the base disease until further investigations.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

  References Top

Hammer H, Korom I. Photodamage of the conjunctiva in patients with porphyria cutánea tarda. Br J Ophthalmol 1992;76:592-3.  Back to cited text no. 1
Sober AJ, Grove AS, Muhlbauer JE. Cicatricial ectropion and lacrimal obstruction associated with the sclerodermoid variant of porphyria cutanea tarda. Am J Ophthalmol 1981;91:396-400.  Back to cited text no. 2
Zaborowski AG, Paulson GH, Peters AL. Sight threatening complications in porphyria cutanea tarda. Eye (Lond) 2004;18:949-50.  Back to cited text no. 3
Sati A, Sangwan VS, Basu S, Kalaiselvan P. Boston keratoprostheis for visual rehabilitation in porphyria cutánea tarda. BMJ Case Rep 2013;2013:bcr2012008267.  Back to cited text no. 4
Gogri PY, Misra NS, Misra S. Ocular manifestations in porphyria cutanea tarda. BMJ Case Rep 2014;2014:bcr2013010402.  Back to cited text no. 5
Altiparmak UE, O flu Y, Kocaoglu FA, Katircioglu YA, Duman S. Ocular complications in 2 cases with porphyria. Cornea 2008;27:1093-6.  Back to cited text no. 6
Takamura N, Kurihara K, Yamashita S, Kondo M. Need for measurement of porphyrins in teardrops in patients with congenital erythropoietic porphyria. Br J Ophthalmol 2002;86:1188.  Back to cited text no. 7
Agarwal S, Majumder PD, Srinivasan B, Iyer G. Scleral necrosis in congenital erythropoietic porphyria: A casereport and review of the literature. Oman J Ophthalmol 2015;8:200-4.  Back to cited text no. 8
[PUBMED]  [Full text]  
Arya SK, Raj A, Kohli P, Bamotra RK. Total corneal melt in patient with porphyria cutanea tarda in presence of another risk factor. Ocul Immunol Inflamm 2018:1-4. doi: 10.1080/09273948.2017.1421231.  Back to cited text no. 9
Bleasel NR, Varigos GA. Porphyria cutanea tarda. Australas J Dermatol 2000;41:197-206.  Back to cited text no. 10
Desnick R, Astrin K. Congenital erythropoietic porphyria: Advances in pathogenesis and treatment. Br J Haematol 2002;117:779-95.  Back to cited text no. 11
Katugampola R, Badminton M, Finlay A, Whatley S, Woolf J, Mason N, et al. Congenital erythropoietic porphyria: A single-observer clinical study of 29 cases. Br J Dermatol 2012;167:901-13.  Back to cited text no. 12
Fritsch C, Bolsen K, Ruzicka T, Goerz G. Congenital erythropoietic porphyria. J Am Acad Dermatol 1997;36:594-610.  Back to cited text no. 13
Veenashree M, Sangwan V, Vemuganti G, Parthasaradhi A. Acute scleritis as a manifestation of congenital erythropoietic porphyria. Cornea 2002;21:530-1.  Back to cited text no. 14
Pandhi D, Suman M, Khurana N, Reddy BS. Congenital erythropoietic porphyria complicated by squamous cell carcinoma. Pediatr Dermatol 2003;20:498-501.  Back to cited text no. 15


  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5]

  [Table 1], [Table 2]


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