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Ocular manifestations in Kindler syndrome

We aimed describe the chronic ocular sequelae of Kindler syndrome. All cases of Kindler syndrome with ocular involvement that presented to a tertiary eye care center were included. Three cases of Kindler syndrome with ocular changes were reviewed. Case 1 (10 years, female) had recurrent epithelial breakdown with severe dry eye and corneal opacity secondary to keratitis. Case 2 (28 years, male) had symblepharon , ocular surface keratinization , and severe dry eye. Case 3 (16 years , female ) had partial limbal stem cell deficiency with dry eye. All cases were treated with topical lubricants, short course of low-potency steroids and immuno-modulators. Attention must be paid to the eye in addition to the oro-an-genital mucosa to avoid longterm ocular sequelae.

Herein, we present three such cases where the patient presented with features suggestive of a chronic ocular disease process that was poorly managed in the initial stage of the disease.

Case Reports
Case 1 A 10-year-old female presented with pain, redness, watering, and diminution of vision in the right eye for 20 days. There was a history of recurrence of similar episodes in the past. She had a visual acuity of hand movement and 6/6 in the right and left eyes, respectively. The right eye revealed a central corneal epithelial defect, 6 x 6 mm in size, with nebulo-macular corneal opacity in the surrounding cornea and 360-degree superficial vascularization [ Fig. 1a and 1b]. The left eye had a normal anterior segment; however, the tear film height was <0.5 mm with punctate staining [ Fig. 1c and 1d]. The tear film breakup time (TBUT) was instantaneous in the left eye, and Schirmer II test revealed values of 4 and 5 mm in the right and left eyes, respectively. Systemic examination revealed hypo-and hyper-pigmented patches (poikiloderma) with cutaneous atrophy of the dorsal surface of the arms, the hand, the foot and legs, pseudoainhum of the fourth and fifth digits of the toe, facial skin atrophy, and hyper-and hypo-pigmentation patches with scaling. The patient was started on topical antibiotics, lubricants, and low-potency steroids in the right eye. Lubricants and cyclosporine 0.05% were started in the left eye. Because there was no improvement, amniotic membrane transplantation was performed to aid epithelial healing [ Fig. 2a], and complete healing was noted at 3 weeks follow-up [ Fig. 2b and 2c].

Case 2
A 28-year-old male presented with a loss of vision in both the eyes for the past 10 years. A history of recurrent episodes of pain, redness, and watering was present, for which he was treated with topical antibiotics and lubricants by the primary physician. At presentation, the visual acuity was perception of light in both the eyes. Slit lamp examination of the right eye showed nebulo-macular corneal opacity, ectasia, and 360-degree superficial vascularization [ Fig

Case 3
A 16-year-old female presented with complaints of foreign body sensation and irritation in both the eyes since childhood. The visual acuity in both the eyes was 6/6 with Schirmer II of 4 and 5 mm in the right and left eyes, respectively, and TBUT of 5 and 6 seconds. Slit lamp examination revealed a reduced tear film height with partial limbal stem cell deficiency. Systemic features were similar to the findings noted in the above two cases. The patient was started on a short course of topical steroids, cyclosporine, and lubricants.
The family history was negative in all the cases.

Discussion
Kindler syndrome, a variant of epidermolysis bullosa, is a skin-blistering disorder that usually presents at birth. [10] It is caused by FERMT1 gene mutation that encodes kindlin-1 protein. [10,11] This protein is responsible for cell-cell adhesion, cell signaling, differentiation, morphogenesis, and migration. Hence, abnormality of kindlin-1 protein results in skin blisters because of cleavage at multiple skin planes. [10] Photo-sensitivity, progressive poikiloderma, and cutaneous atrophy are the striking features of this disorder, which helps to distinguish it from other skin-blistering disorders. [5] The extra-cutaneous features include gingivitis, colitis, mucosal stenosis, syndactylyl, poor dentition, and nail dystrophy. [2,7] Ocular manifestations may result from both the primary kindling-related loss of corneal epithelial integrity and exposure keratopathy because of eyelid malposition. The reported clinical features include cicatricial ectropion, kerato-conjunctivitis, conjunctival scarring, blepharitis, recurrent corneal erosions, corneal opacity, corneal ectasia, symblepharon, pigment deposits over the lens capsule, and segmental chorioretinal atrophy. [3,5,8,9]  In our case series, we observed kindler syndrome with ocular involvement of varying severity. Kerato-conjunctivitis sicca and limbal stem cell deficiency were common to all. In addition, case 1 had corneal opacity as a result of recurrent epithelial breakdown, and case 2 had a keratinized ocular surface with symblepharon, entropion, and trichiasis. It is important to note that none of the patients were referred to an ophthalmologist for screening of ocular involvement on confirmation of the diagnosis of Kindler syndrome. We suspect that a timely screening of these cases and initiation of appropriate therapy could have salvaged vision in these young patients. This was missed in all our cases by the primary treating physician.

Conclusion
To conclude, Kindler syndrome can have ocular involvement of variable severity early in their life. Hence, a timely referral at the confirmation of diagnosis to an ophthalmologist for screening is a must.

Meeting presentation
Poster presentation at KERACON 2019.

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.