Case Series: Management of Neurotrophic Keratitis from Familial Dysautonomia

Abstract

SIGNIFICANCE:

Familial dysautonomia is a rare genetic disorder that affects the sensory and autonomic nervous systems. Affected individuals have decreased corneal sensation and can develop serious complications from neurotrophic keratitis. Scleral devices are an excellent option for the long-term management of patients with familial dysautonomia and neurotrophic keratitis.

PURPOSE:

In this series, we describe three patients with familial dysautonomia and classic ocular complications fit with scleral devices. No identifiable health information is included in this case report.

CASE REPORTS:

Case 1: A 35-year-old white male presented with blurred vision without complaint of pain or dryness. He had moderate punctate corneal staining and central stromal corneal scarring in both eyes despite use of artificial tears, punctal plugs, and therapeutic soft lenses. He was fit with 18.2-mm commercial scleral devices, which improved vision and protected the ocular surface. Case 2: A 20-year-old cognitively impaired white female presented with history of frequent eye rubbing and self-mutilation. She had recurrent corneal abrasions with corneal scarring in both eyes and was fit with 16-mm gas-permeable prosthetic replacement of the ocular surface ecosystem devices. Case 3: An 18-year-old white male with history of frequent corneal abrasions and blurred vision was referred by his medical doctor. He and his mother were trained in the safe handling of 16- and 16.5-mm gas-permeable prosthetic replacement of the ocular surface ecosystem devices in the right and left eyes. Corneal epithelial defects healed and vision improved with daily use.

CONCLUSIONS:

Individuals with familial dysautonomia present unique clinical challenges owing to severe ocular surface disease and inability to perceive pain. Initial therapy for neurotrophic keratitis includes lubrication, punctal occlusion, and therapeutic lenses. Additional therapies include autologous serum tears, amniotic membrane treatment, scleral devices, and tarsorrhaphy. In this series, scleral devices are an excellent option to protect the ocular surface and prevent common ocular complications.

Graphical Abstract

Familial dysautonomia, also known as hereditary sensory and autonomic neuropathy type III or Riley-Day syndrome, is an autosomal recessive genetic disorder that disrupts the nervous system cells in the autonomic nervous system, controlling involuntary actions, and sensory nervous system, controlling activities associated with the senses.¹ It is a rare genetic disease caused by a mutation of the IKBKAP gene that is most common in people of Ashkenazi Jewish descent, affecting 1 in 3700.¹ This mutation affects prenatal neuronal development causing symptoms from birth.¹ Affected individuals have insufficient neuronal development and advanced neuronal degeneration.² This debilitating disease has a high mortality rate, with only about 50% of affected individuals surviving to age of 30 years with frequent hospitalizations due to electrolyte imbalance, respiratory exacerbations, and injury to muscle and bone.³ Early signs include poor growth and muscle tone, difficulties with feeding, frequent lung infections, and lack of tear production.¹ Most individuals experience delay in developmental milestones such as walking and speech.¹

Common ocular findings in familial dysautonomia include corneal disease, myopia, strabismus, and optic atrophy.² Affected individuals typically have neurotrophic corneas involving both eyes, a degenerative condition due to trigeminal nerve impairment, and decreased tear production.^3,4 This decreased corneal sensation puts the cornea at constant risk of punctate keratitis, persistent epithelial defect, corneal ulcer, and stromal melt.^4,5 Treatment of neurotrophic keratitis aims to prevent additional corneal damage and support corneal healing. This includes eliminating medications that can cause neurotrophic keratitis, such as antihistamines and neuroleptics, in addition to preserved topical medications.³ Primary treatment begins with aggressive lubrication with preservative-free artificial tears, prophylactic topical antibiotics, silicone punctal plugs, and therapeutic soft lenses.³ Additional treatment options include amniotic membrane transplantation, tarsorrhaphy, and scleral devices.³ Studies are also investigating autologous serum tears, umbilical cord serum eye drops, and neurotrophin eye drops to restore corneal nerve damage.³ Patients with neurotrophic corneas require close monitoring because they are at constant risk of corneal abrasions as well as persistent epithelial defects and infection and may be unable to recognize or report problems.⁴

CASE SERIES

In the following cases, we discuss the use of scleral devices to stabilize the ocular surface in three patients with familial dysautonomia confirmed by genetic testing. Considerations made when fitting a patient with scleral devices include visual potential, severity of disease, and available caregiver support.

Case 1

A 35-year-old white male with familial dysautonomia was referred by his cornea specialist for evaluation. He complained of blurred vision worse in the right eye and history of frequent eye infections. Notably, he had no complaints of dryness or eye pain. Previous treatments included preservative-free artificial tears every 2 hours, 0.05% topical cyclosporine twice daily, therapeutic soft lenses, and silicone plug punctal occlusion. His entering best-corrected visual acuity was 20/80 and 20/200 in the right and left eyes. The right eye had trace diffuse conjunctival injection, moderate diffuse punctate epithelial erosions, an elevated central scar measuring 3 × 3 mm, and diffuse corneal haze. His left eye had trace diffuse conjunctival injection, moderately severe diffuse punctate epithelial erosions, and moderate diffuse corneal stromal haze.

Treatment goals included ocular surface support and visual improvement that was limited by corneal scarring and irregular astigmatism. Therapeutic options were discussed with the patient including frequent lubrication, commercial scleral device, and prosthetic replacement of the ocular surface ecosystem (PROSE) treatment. The patient requested commercial scleral fitting first because of lower cost. The diagnostic lenses were Jupiter scleral devices 18.2 mm in diameter (Essilor Contacts, Dallas, TX) with 7.5 base curve in both eyes. The patient and his mother were immediately trained on safe handling and disinfection. He was instructed to return wearing his devices for 6 hours. At this time, there were adequate central corneal clearance, complete limbal clearance, and scleral alignment. After device removal, there was no corneal punctate or conjunctival staining. During his 3-month follow-up visit, he reported better vision with 12- to 14-hour device wear time daily. Although limited by corneal scarring, corneal staining resolved in both eyes, and his vision improved to 20/40 in the right eye and 20/70 in the left eye.

Case 2

A 20-year-old cognitively impaired white female with familial dysautonomia and autism presented to the clinic with her family and full-time nurse. The patient’s mother and nurse reported she wore safety glasses owing to history of frequent eye infections with recurrent corneal abrasions due to eye scratching and self-mutilation. Her ocular history included multiple corneal abrasions per year starting at age of 2 years with corneal scarring in both eyes. Her current treatment included preservative-free artificial tears and topical antibiotic ointment each instilled twice daily. Traditional visual acuities were not able to be obtained; however, the patient demonstrated ability to interact with her visual communication board. The examination was difficult with the patient falling asleep, although limited retinoscopy revealed a dim reflex in both eyes, and examination with portable biomicroscope showed mild lid and lash scurf, white and quiet bulbar conjunctiva, mild inferior corneal stromal neovascularization, mild stromal scarring, and moderate diffuse corneal punctate epithelial erosions without epithelial defects in both eyes. Treatment options discussed included continued frequent lubrication versus commercial scleral devices or prosthetic replacement of the ocular surface ecosystem devices (BostonSight, Needham, MA). They elected to proceed with prosthetic replacement of the ocular surface ecosystem treatment given the benefits of customization for a noncommunicative patient unable to feel or express pain. Initially, prosthetic replacement of the ocular surface ecosystem diagnostic devices 16 mm in diameter was applied with fluorescein in the bowl to ensure full corneal clearance with 7.9 base curve in the right and left eyes. Complete clearance of the cornea and limbus without vascular haptic compression was noted. Retinoscopy reflex improved over the devices and was used to order new devices.

Ample time was scheduled for the dispensing visit to fully train the patient’s caregivers on safe device handling. The patient was in a wheelchair with a feeding tube and unable to apply a scleral device herself. Prosthetic replacement of the ocular surface ecosystem device use was recommended during daytime hours only, and the use of additional measures, such as protective goggles at bedtime, was recommended. Her caregivers were asked to closely monitor her for potential complications with increased redness. The patient returned after 6 hours of continuous wear to assess the fit and cornea and conjunctival tissue after device removal. She was able to nod yes when asked if she liked her new devices and interacted well with her communication board. The central clearance was slightly less than one device thickness using portable biomicroscope with no vascular compression in either eye. After device removal, the corneas had no punctate staining. After 2 years, she has continued to use her devices for 10 to 12 hours daily without complication of corneal abrasion or infection. The corneal punctate staining has resolved, and although we were unable to obtain traditional visual acuities, she continues to use her alternative communication devices.

Case 3

An 18-year-old white male presented with his mother complaining of worsening blurry vision and frequent abrasions in both eyes. His familial dysautonomia specialist recommended he be fit with prosthetic replacement of the ocular surface ecosystem devices in both eyes. He was closely followed by a cornea specialist and previously treated with frequent lubrication, 0.05% topical cyclosporine twice daily, partial tarsorrhaphy in both eyes, topical steroids, ointment, therapeutic lenses, and cautery of all four puncta. He reported dryness in both eyes without pain. During his initial visit, best-corrected visual acuity was 20/400 in the right eye and counting fingers at 6 feet in the left eye. He had moderately severe punctate epithelial erosions and a small central epithelial defect in the right eye, as well as moderately severe punctate epithelial erosions with a small central epithelial defect, faint corneal haze, and central stromal scarring in the left eye. He was fit with prosthetic replacement of the ocular surface ecosystem devices, and his vision improved to 20/50 and 20/200 in the right and left eyes with overrefraction. We recommended he continue frequent lubrication, topical cyclosporine, and ciprofloxacin 0.3% daily in both eyes until he returned (Figs. 1 and 2).

FIGURE 1.

Photographs of the right and left eyes, without scleral devices, at follow-up visit without epithelial defect (case 3).

FIGURE 2.

Photographs of the right and left eyes with PROSE devices at the follow-up visit (case 3). PROSE = prosthetic replacement of the ocular surface ecosystem.

A month later, the patient and his mother were both trained in safe handling and disinfection of 16- and 16.5-mm prosthetic replacement of the ocular surface ecosystem devices in the right and left eyes, both with 7.9 base curve. Vision was 20/50 and 20/100 in the right and left eye. After 6 hours of wear, both devices had slight excessive central corneal clearance. The right device had scleral alignment, whereas the left had scleral vascular compression nasal and temporal. There was no epithelial defect or corneal staining on device removal; however, mild conjunctival impression and stain were noted nasally and temporally in the left eye. New devices were ordered with decreased central clearance in both eyes and flatter toric peripheral scleral landing nasal and temporal in the left eye. The patient had an unscheduled visit after being diagnosed with a new corneal abrasion in his right eye. With continued daily prosthetic replacement of the ocular surface ecosystem device use and short-term use of a topical antibiotic, the epithelial defects and punctate staining resolved in both eyes, and best-corrected vision improved to 20/40 in the right eye and 20/100 in the left eye. The patient has maintained daily prosthetic replacement of the ocular surface ecosystem use of 16 hours daily with nightly protective goggle use for 2 years.

DISCUSSION

Although familial dysautonomia is very rare, it is important to recognize that affected individuals need early ophthalmic care to protect the ocular surface and prevent permanent vision loss. Scleral devices can play an important role in stabilizing the ocular surface in patients with neurotrophic keratitis and should be considered in the first decade of life.^6–9 In addition to improving visual function, these devices serve many therapeutic functions. They protect the ocular surface from mechanical forces and promote corneal healing and corneal hydration by maintaining a stable tear film on the ocular surface.¹⁰ Unlike soft therapeutic lenses, scleral devices maintain a constant tear reservoir between the cornea and device, which creates a smooth optical surface. The device is filled with preservative-free saline and fit to completely vault over the cornea, resting entirely on the sclera.

The functional severity scale predicts quality of life and survival in individuals with familial dysautonomia who often have cognitive delays.² There are 10 categories including motor development, cognitive ability, psychological status, expressive speech, balance, oral coordination (how nutrition is obtained), frequency of dysautonomia crises, respiratory status, cardiovascular status, and nutritional status scored from 1 (severe) to 5 (no impairment).⁵ A study of 123 individuals with familial dysautonomia found that lower scores for cardiovascular status and frequency of crisis were associated with lower survival rates.⁵ The patient in case 2 had the most severe disease with frequent autonomic crises and required enteral feedings. Individuals with familial dysautonomia face significant medical challenges and may require adaptive examination techniques and flexible follow-up schedules.

As seen in this case series, successful device use often uses a supportive care team including family and nursing staff. Close medical follow-up is necessary owing to inadequate corneal sensation and risk of infection. Nonhealing epithelial defects can be particularly challenging to manage in individuals with neurotrophic corneas. Scleral devices can also be used to heal corneal epithelial defects as presented in case 2. Previous reports have demonstrated success with a standardized approach of overnight device use with a nonpreserved fourth-generation fluoroquinolone antibiotic using prosthetic replacement of the ocular surface ecosystem treatment.¹¹

Early intervention is key to prevent corneal scarring and vision loss.^8,9 Each of the patients presented with corneal scarring limiting visual potential and likely could have benefited from timely scleral device fitting in childhood. A team-based approach should be considered to ensure safe device application and disinfection with close monitoring of the ocular health. Scleral devices can be an effective way to treat patients with neurotrophic corneas and particularly individuals with familial dysautonomia. Future prospective studies on familial dysautonomia are needed, particularly focusing on early intervention in pediatric patients.