TACSTD2-Related Gelatinous Drop-like Corneal Dystrophy: An Asymmetrical Exception
Clinical Genetics and Therapeutics
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Primary Categories:
- Clinical- Pediatric
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Secondary Categories:
- Clinical- Pediatric
Introduction
Gelatinous drop-like corneal dystrophy (GDLD) is an autosomal recessive condition characterized by subepithelial and stromal amyloid deposition leading to corneal opacity that is typically bilateral. Recurrence is common despite intervention and visual acuity is significantly reduced by the third decade of life. Maeno et al. (2022), described an individual with GDLD with unilateral, recurring, corneal opacity with an asymptomatic second eye.
Case Presentation
A 7-year-old female was referred to Wills Eye Cornea service for corneal clouding of the left eye, associated with light sensitivity and discomfort. Due to unilateral presentation and history of frequent cold sores, she was treated by the pediatric ophthalmologist with Acyclovir for presumed herpes simplex virus 1 (HSV) keratitis. External exam revealed mild blepharitis and mild papillae in the inferior palpebral conjunctiva of both eyes. Corneal examination of the right eye was unremarkable. Corneal examination of the left eye was significant for a 4mm v x 3.5mm area of anterior stromal scarring and haze with overlying irregular epithelium, which showed punctate staining with fluorescein. No definitive dendritic lesions were noted. The posterior exam of both eyes was unremarkable.
Diagnostic Workup
Histopathologic evaluation of superficial keratectomy revealed suebepithelial amyloid deposition. Primary systemic amyloidosis evaluation was completed with a pediatric nephrologist and cardiologist and was unrevealing. Genetic testing was completed via a next generation sequencing multigene panel for corneal dystrophy and revealed a homozygous likely pathogenic variant in TACSTD2 (NM_002353.2): c.703_704del, p.(Leu235Ilefs*141). This is consistent with a diagnosis of GDLD.
Treatment and Management
Following initial superficial keratectomy, a second superficial keratectomy was performed in the left eye 6 months later for recurrence of subepithelial amyloid deposits. The patient developed a 3rd recurrence of dystrophy, for which she will undergo a 3rd superficial keratectomy procedure. Penetrating keratoplasty is not being pursued at this time due to likelihood of recurrence in this condition.
Outcome and Follow-Up
Three inferior, scattered lesions are now present in the right eye. The disease remains very asymmetrical. Management is supportive and keratectomy will continue to be completed as needed. Corneal evaluation and genetic testing for siblings is recommended.
Discussion
Here, we present a case of gelatinous drop-like corneal dystrophy in a pediatric patient, initially with unilateral findings, and eventual involvement of the second eye two years later. GDLD is a rare, autosomal recessive disease that can present asymmetrically and be mistaken for other etiologies. Genetic testing has utility in corneal dystrophy as a diagnosis can provide information on prognosis, management, and recurrence risk.
Conclusion
GDLD is a rare, autosomal recessive condition that should be considered in cases of unilateral or asymmetrical corneal opacity with amyloid deposits.
Gelatinous drop-like corneal dystrophy (GDLD) is an autosomal recessive condition characterized by subepithelial and stromal amyloid deposition leading to corneal opacity that is typically bilateral. Recurrence is common despite intervention and visual acuity is significantly reduced by the third decade of life. Maeno et al. (2022), described an individual with GDLD with unilateral, recurring, corneal opacity with an asymptomatic second eye.
Case Presentation
A 7-year-old female was referred to Wills Eye Cornea service for corneal clouding of the left eye, associated with light sensitivity and discomfort. Due to unilateral presentation and history of frequent cold sores, she was treated by the pediatric ophthalmologist with Acyclovir for presumed herpes simplex virus 1 (HSV) keratitis. External exam revealed mild blepharitis and mild papillae in the inferior palpebral conjunctiva of both eyes. Corneal examination of the right eye was unremarkable. Corneal examination of the left eye was significant for a 4mm v x 3.5mm area of anterior stromal scarring and haze with overlying irregular epithelium, which showed punctate staining with fluorescein. No definitive dendritic lesions were noted. The posterior exam of both eyes was unremarkable.
Diagnostic Workup
Histopathologic evaluation of superficial keratectomy revealed suebepithelial amyloid deposition. Primary systemic amyloidosis evaluation was completed with a pediatric nephrologist and cardiologist and was unrevealing. Genetic testing was completed via a next generation sequencing multigene panel for corneal dystrophy and revealed a homozygous likely pathogenic variant in TACSTD2 (NM_002353.2): c.703_704del, p.(Leu235Ilefs*141). This is consistent with a diagnosis of GDLD.
Treatment and Management
Following initial superficial keratectomy, a second superficial keratectomy was performed in the left eye 6 months later for recurrence of subepithelial amyloid deposits. The patient developed a 3rd recurrence of dystrophy, for which she will undergo a 3rd superficial keratectomy procedure. Penetrating keratoplasty is not being pursued at this time due to likelihood of recurrence in this condition.
Outcome and Follow-Up
Three inferior, scattered lesions are now present in the right eye. The disease remains very asymmetrical. Management is supportive and keratectomy will continue to be completed as needed. Corneal evaluation and genetic testing for siblings is recommended.
Discussion
Here, we present a case of gelatinous drop-like corneal dystrophy in a pediatric patient, initially with unilateral findings, and eventual involvement of the second eye two years later. GDLD is a rare, autosomal recessive disease that can present asymmetrically and be mistaken for other etiologies. Genetic testing has utility in corneal dystrophy as a diagnosis can provide information on prognosis, management, and recurrence risk.
Conclusion
GDLD is a rare, autosomal recessive condition that should be considered in cases of unilateral or asymmetrical corneal opacity with amyloid deposits.