Axenfeld - Rieger syndrome with spontaneous hyphema – A rare presentation and its association with COL4A1 mutation

Vijayalakshmi A Senthilkumar; Shiva M Krishna; Chitaranjan Mishra; Ayushi Sinha

doi:10.4103/tjosr.tjosr_124_21

PHOTO ESSAY

Year : 2022 | Volume : 60 | Issue : 1 | Page : 101-103

Axenfeld - Rieger syndrome with spontaneous hyphema – A rare presentation and its association with COL4A1 mutation

Vijayalakshmi A Senthilkumar¹, Shiva M Krishna¹, Chitaranjan Mishra², Ayushi Sinha³
¹ Department of Glaucoma, Aravind Eye Hospital and Postgraduate Institute of Ophthalmology, Madurai, Tamil Nadu, India
² Department of Retina, Aravind Eye Hospital and Postgraduate Institute of Ophthalmology, Madurai, Tamil Nadu, India
³ Department of Retina, Aravind Eye Hospital, Puducherry, India

Date of Submission	08-Aug-2021
Date of Decision	26-Sep-2021
Date of Acceptance	28-Sep-2021
Date of Web Publication	22-Mar-2022

Correspondence Address:
Dr. Vijayalakshmi A Senthilkumar
Department of Glaucoma, Aravind Eye Hospital and Postgraduate Institute of Ophthalmology, Madurai, Tamil Nadu
India

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/tjosr.tjosr_124_21

Abstract

We report an unusual presentation of spontaneous hyphema in a young male with Axenfeld − Reiger syndrome (A-R syndrome) and developmental glaucoma. This rare presentation of A-R syndrome with spontaneous hyphema and dilated iris vasculature has been reported in mice eyes with COL4A1 mutation, but not in human eyes.

Keywords: Axenfeld − Reiger syndrome, COL4A1, spontaneous hyphema

How to cite this article:
Senthilkumar VA, Krishna SM, Mishra C, Sinha A. Axenfeld - Rieger syndrome with spontaneous hyphema – A rare presentation and its association with COL4A1 mutation. TNOA J Ophthalmic Sci Res 2022;60:101-3

How to cite this URL:
Senthilkumar VA, Krishna SM, Mishra C, Sinha A. Axenfeld - Rieger syndrome with spontaneous hyphema – A rare presentation and its association with COL4A1 mutation. TNOA J Ophthalmic Sci Res [serial online] 2022 [cited 2022 Jun 29];60:101-3. Available from: https://www.tnoajosr.com/text.asp?2022/60/1/101/340346

Case Report

A 32-year-old young male presented with painless defective vision in the right eye (RE) of 5 days duration. The patient was a diagnosed case of A-R syndrome with bilateral developmental glaucoma since the age of 9 years, underwent sequential glaucoma filtering surgery (trabeculectomy) in both eyes (BE) at the age of 10 years. He was on steady follow-up, with no complications and stable intraocular pressures (IOP) of 10–15 mmHg in RE; however, the left eye (LE) ended up with glaucomatous optic atropy. There was no history of ocular trauma, oral anticoagulant usage, bleeding disorder, and smoking. At presentation, BCVA was 6/12 in RE and perception of light (PL) with inaccurate projection of rays in LE and IOP was 14 mmHg RE, 15 mmHg LE. Slit-lamp examination RE showed fibrosed bleb, microcornea, posterior embryotoxon, 2 mm hyphema in anterior chamber, ectropion uveae, patent surgical iridectomy, dilated iris stromal vessels from 4 O'clock to 6 O'clock, and pseudophakia [Figure 1]a and [Figure 1]b. LE showed failed bleb, corectopia, stretch iris hole, brown nuclear cataract [Figure 2]a and [Figure 2]b. Gonioscopy RE did not reveal any neovascularization but showed angle dysgenesis [Figure 3]a and [Figure 3]d. Dilated fundus examination RE revealed tilted disc and cup-disc ratio of 0.9.

Figure 1: (a) Slitlamp photograph right eye showing fibrosed bleb, microcornea, hyphema, patent surgical iridectomy at 12 O'clock, psuedophakia. (b) Dilated iris stromal vessels from 4 O'clock to 6'0 clock (white arrows)

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Figure 2: (a and b) Slit-lamp photograph of the left eye showing failed bleb, corectopia, stretch iris hole, peripheral anterior synechiae superiorly, brown nuclear cataract

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Figure 3: (a-d) Gonioscopy right eye showing angle dysgenesis without any neovascularization

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Fundus-Iris-Fluorescein-Angiography performed to rule out any evidence of ischemia/neovascularization was unremarkable [Figure 4]a and [Figure 4]b. Ultrasound biomicroscopy and B-mode ultrasonography done to exclude any intraocular tumors also turned out to be normal. Blood investigations including liver and renal function tests, carotid Doppler, and cardiac profile were within the normal limits. The patient was reassured and treated conservatively with topical steroids and cycloplegics along with antiglaucoma medications for 2 weeks. The hyphema resolved completely with BCVA of 20/20 in RE at 2 weeks follow-up [Figure 5]a and [Figure 5]b.

Figure 4: (a) Iris angiography showing normal study, (b) fundus angiography showing normal study, no neovascularization/leakage

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Figure 5: (a and b) Slit-lamp photograph right eye at 2 weeks' follow-up showing resolved hyphema

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Discussion

A-R syndrome are a group of bilateral congenital anomalies and approximately 50%–75% of patients are associated with early onset and aggressive glaucoma.^[1] Hyphema can happen following trauma, secondary to uveitis, neovascularization, anticoagulants, valsalva-maneuvers, iris melanomas, intraocular tumors, Juvenile xanthogranuoma, uveitis-glaucoma-hyphema syndrome, and iris microhemangiomas (Cobb's hemangiomas).^[2] All these clinical entities were ruled out by meticulous clinical and systemic examination. Other possibility being neovascularization at the edges of ostium similar to Swan syndrome which was ruled out on fluorescein angiography.^[3] A possibility of spontaneous hyphema was made, as a single case report was reported in the literature.^[4]

A-R syndrome is a multigenic disorder associated with mutations in CYP1B1, FOXC1, FOXC2, FOXE3, LMBX1B, MAF, PAX6, PITX2, and PITX3. Independent mutagenesis screens in mice showed developing eyes from COL4A1 mutation presented with anterior chamber hyphema, iridocorneal adhesions, dysgenesis of the angle structures and ciliary body, dilated iris vasculature (as was seen in our patient) postulating the vascular contribution of COL4A1.^[5] Genetic analysis was not done in our patient due to financial constraints. Future genetic studies are needed for better understanding of vascular contribution of COL4A1 mutation in patients with A-R syndrome.

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

Nil.

Conflicts of interest

There are no conflicts of interest.

References

1.	Gould DB, Marchant JK, Savinova OV, Smith RS, John SW. Col4a1 mutation causes endoplasmic reticulum stress and genetically modifiable ocular dysgenesis. Hum Mol Genet 2007;16:798-807.
2.	Goyal S, Foster PJ, Siriwardena D. Iris vascular tuft causing recurrent hyphema and raised IOP: A new indication for laser photocoagulation, angiographic follow-up, and review of laser outcomes. J Glaucoma 2010;19:336-8.
3.	Swan KC. Hyphema due to wound vascularization after cataract extraction. Arch Ophthalmol 1973;89:87-90.
4.	Dhingra D, Kulshrestha A, Kaushik S. Axenfeld Rieger Anomaly Presenting as Spontaneous Hyphema. Ophthalmol Glaucoma. 2018;131.
5.	Mao M, Kiss M, Ou Y, Gould DB. Genetic dissection of anterior segment dysgenesis caused by a Col4a1 mutation in mouse. Dis Models Mech 2017;10:475-85.