Ocular Manifestations of Alport Syndrome: A Case Report

Abstract:

Background: Alport syndrome is a rare genetic disorder affecting the kidneys, eyes, and ears due to mutations in type IV collagen genes. Anterior lenticonus is a characteristic ocular manifestation and can serve as an early diagnostic sign. This case highlights the role of ophthalmic evaluation in the early detection and management of Alport syndrome.

Case Report: A 26-year-old male presented with progressive vision deterioration and poor night vision. Ocular examination revealed high myopia, astigmatism, bilateral anterior lenticonus, and posterior polar cataract. Systemic evaluation confirmed nephritis and bilateral partial hearing loss, leading to a diagnosis of Alport Syndrome. The patient underwent sequential lens extraction with intraocular lens (IOL) implantation in both eyes, resulting in significant visual improvement. Regular nephrology, audiology, and ophthalmology follow-ups were advised. 

Conclusion: This case emphasizes the significance of early ophthalmic findings in diagnosing systemic diseases like Alport Syndrome. Anterior lenticonus is a key indicator that warrants further systemic evaluation. A multidisciplinary approach, including nephrologists, audiologists, and genetic counsellors, is essential for comprehensive patient management. Early intervention and continued monitoring are crucial to preserving vision and managing systemic complications.

Keywords: Alport Syndrome; Gene Mutation; Type IV Collagen; Bilateral Anterior Lenticonus; Posterior Polar Cataract.

Background

Alport syndrome refers to a collection of diverse genetic illnesses that impact the basement membrane of the kidney and frequently involve the cochlea and the eye 1,2. Alport syndrome, or hereditary nephritis, is a genetic condition caused by mutations in the genes encoding alpha-3, alpha-4, and alpha-5 chains of type IV collagen (COL4A3, COL4A4, COL4A5) or the collagen IV α345 network3. Approximately 80% of men with XLAS develop some hearing loss until they reach their teenage years4. Ocular manifestations of Alport syndrome include anterior lenticonus, dot-and-fleck retinopathy, and posterior polymorphous corneal dystrophy. Anterior lenticonus, a conical protrusion of the lens, is a hallmark feature and often leads to progressive vision impairment. The lens capsule in Alport syndrome individuals, particularly males, becomes weakened and deficient in mechanical integrity, leading to a distortion of the lens shape over time, appearing as anterior lenticonus, characterized by the protrusion of the central lens into the anterior chamber5–8. Since collagen is an essential protein in the eyes, vital for the clarity of the cornea, sclera, and the process of wound healing, mutations in COL4A3-5 in people with Alport syndrome would likely lead to a decline in vision9. Given the hereditary nature of the illness, numerous previous researchers have sought to explore the potential of gene therapy as a treatment option 10. It should be emphasized that gene therapy will not address the modifications that transpire during the fatal and early developmental stages of the condition.

Case Report 

A 26-year-old male arrived for a standard ocular examination. His primary concerns were a progressive decline in vision over 11 years and impaired night vision despite the use of spectacles. His ocular history indicated a six-year dependence on glasses. He denied any reports of floaters or flashes. He underwent a kidney transplant systematically ten years ago. The patient's main concerns were the gradual deterioration of his vision and the challenges he encountered with visual tasks, particularly in dim lighting. The symptoms necessitated a comprehensive ocular and systemic assessment to ascertain the underlying cause and adequately manage the condition.

Diagnostic Procedure

1. Visual Acuity Assessment: Visual acuity was measured using a Snellen chart at both distance and near, revealing OD is 6/18p and OS is 6/24 and for near N12 for both eyes.

2. Objective refraction: Refraction tests revealed significant myopia and astigmatism, with objective refraction showing OD -9.25/-2.50x10 and OS -10.50/-3.00x135.

3. Subjective refraction: Subjective acceptance of refraction was slightly better, with OD -8.50/-2.00x20 (6/9p) and OS -9.75/-2.50x120 (6/12p). 

4. Slit lamp examination: A detailed slit lamp examination was performed to evaluate the anterior and posterior segments of the eye. The examination revealed bilateral anterior lenticonus, a conical protrusion of the lens, along with posterior polar cataracts in both eyes. The cornea, conjunctiva, and anterior chamber appeared normal, but the pupils were slightly miotic (2mm). The presence of anterior lenticonus, a hallmark feature of Alport syndrome, raised suspicion of a genetic disorder.

5. Cycloplegic refraction: Cycloplegic refraction was conducted to obtain a more accurate measurement of the patient’s refractive error by temporarily paralyzing the ciliary muscle. During retinoscopy, an oil drop reflex was observed at the centre of the lens, a characteristic finding in anterior lenticonus. The objective refraction under cycloplegia showed a significant difference (10D) between dry and wet retinoscopy, with OD +1.75/+0.50x20 and OS +2.50/+1.00x90. Subjective acceptance of refraction under cycloplegia was OD +1.50D (6/12p) and OS +2.00D (6/18). This confirmed the presence of a high refractive error and lenticonus, which are typical features of Alport syndrome.

6. Special Diagnostic Test: To further evaluate the structural abnormalities, specialized diagnostic tests were performed. A-scan Biometry was used to measure the axial length of the eye and confirm the presence of lens abnormalities. Ultrasound Biomicroscopy (UBM) provided detailed imaging of the anterior segment, highlighting the conical protrusion of the lens (anterior lenticonus). A dilated fundus examination was also conducted, which revealed peripheral drusen but no significant abnormalities in the optic disc or macula. These tests collectively confirmed the structural changes associated with Alport syndrome and provided a clearer picture of the extent of ocular involvement.

7. Systemic investigation: Given the ocular findings and the patient’s history of renal transplantation, systemic investigations were initiated to confirm the diagnosis of Alport syndrome. An ENT evaluation revealed bilateral partial hearing loss, a common extrarenal manifestation of the syndrome. A nephrology consultation confirmed the presence of nephritis, consistent with the renal involvement seen in Alport syndrome. Genetic counselling was recommended to assess the hereditary nature of the condition and to screen family members for potential involvement. These systemic findings, along with the ocular abnormalities, led to a definitive diagnosis of Alport syndrome and highlighted the need for a multidisciplinary approach to management.

Diagnosis:

After a thorough diagnosis, the patient was diagnosed with Alport syndrome, a rare genetic illness that causes renal failure, hearing loss, and ocular problems. The syndrome was confirmed by bilateral anterior lenticonus and posterior polar cataracts, as well as retinal peripheral drusen. Alport syndrome's extrarenal symptoms nephritis and bilateral partial hearing loss were verified by systemic tests. His kidney transplant history supported the diagnosis. To determine if the illness is inherited and screen family members, genetic counselling was advised.

Prognosis:

The prognosis for people with Alport syndrome is dependent upon the severity of renal, auditory, and ocular involvement. Timely diagnosis and action may delay conditions progression. The condition is progressive, necessitating lifetime multidisciplinary treatment for individuals. The patient's vision markedly improved after surgery; however, consistent follow-ups are crucial to assess renal and auditory functions.

  Treatment plan:

1. Surgical Intervention: The patient underwent surgical treatment, commencing with lens extraction and intraocular lens (IOL) implantation in the left eye (OS). This was prioritized due to the patient's considerable vision impairment. One month later, the identical treatment was conducted on the right eye (OD) to facilitate a balanced and sequential recovery, hence reducing postoperative problems.

2. Post-Operative Prescription: Postoperative refraction showed significant improvement, with the left eye achieving near-normal vision (6/6) and the right eye improving to 6/12 initially, and later to 6/6 after the second surgery. After to the surgical procedures, the patient was prescribed corrective eyewear to enhance visual acuity. The prescription specified OD -0.75/-1.50×100, OS -0.50/-0.75×90, and NV: BE +3.00 DS for near vision. This facilitated superior medical refractive correction and good functional vision.

3. Systemic Management and Multidisciplinary Care: Due to the systemic characteristics of Alport syndrome, the patient was referred to other specialists for thorough management. Regular meetings with a nephrologist were arranged to assess renal function, given the patient's history of kidney transplantation and nephritis. An audiologist was engaged to address the bilateral partial hearing loss. The patient was also instructed to occasionally consult a transplant surgeon to monitor the stability of the renal transplant. This multidisciplinary approach guaranteed that every aspect of the syndrome was considered.

4. Genetic Counselling and Family Screening: Genetic counselling was advised for the patient and his relatives to comprehend the hereditary aspects of Alport syndrome. Due to the disorder being attributed to abnormalities in the genes responsible for encoding type IV collagen, family members were recommended to undergo screening for early detection and therapy. Genetic counselling offered insights into the dangers of transmitting the illness to subsequent generations and examined possible prevention strategies. This step was essential for the enduring management of the syndrome inside the family.

5. Follow-up and Long-Term Monitoring: The patient was instructed to be involved in regular follow-up appointments to assess ocular and systemic health. Ophthalmologic and optometric evaluations were arranged quarterly to evaluate visual acuity, intraocular lens stability, and any possible consequences. The patient was also advised to undergo multidisciplinary consultations every six months, including a nephrologist, audiologist, and transplant surgeon. The significance of compliance with follow-up appointments was underscored to facilitate quick recognition and management of complications associated with Alport syndrome.

Discussion:
Alport syndrome is a multisystem condition necessitating a collaborative strategy among ophthalmologists, optometrist, nephrologists, and audiologists. The occurrence of anterior lenticonus and posterior polar cataract in this patient aligns with the ocular signs of Alport syndrome. The notable enhancement in visual acuity following IOL implantation highlights the necessity of early surgical intervention. The patient's systemic problems, such as nephritis and hearing loss, underscore the importance for continuous multidisciplinary care. Genetic counselling is essential for family members to recognize and address probable situations rapidly.

Conclusion:

This case emphasizes the significance of an extensive diagnostic and treatment strategy in the management of Alport syndrome. Early identification of ocular anomalies, along with timely surgical surgery, can significantly enhance patients' quality of life. Consistent follow-ups and interdisciplinary care are crucial to manage the systemic signs of the disease. Genetic counselling and familial screening are essential in the prevention and management of this genetic condition.

This case report is constrained by focusing on a single patient, hence limiting the applicability of the findings to the wider population affected by Alport syndrome. The study is deficient in long-term follow-up data, limiting the evaluation of the sustainability of surgical outcomes and the advancement of systemic problems over time. The paper also fails to examine the potential diversity in treatment responses among patients with varying genetic mutations or illness severities. The lack of a control group or comparative research with alternative treatment modalities restricts the capacity to formulate solid findings regarding the appropriate management plan for Alport syndrome.

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