Introduction 

Parry-Romberg syndrome (PRS) is a rare and progressive disorder that affects the skin and nervous system (neurocutaneous) as well as the skull and facial bones (craniofacial). PRS is recognised by the wasting and atrophy of one half of the face, which has a predominance in children and young adults. The atrophy can extend beyond the skin and into tissue, muscle, and even bone.^1,2

PRS usually has an early onset of eye (ophthalmologic) complications. It has an approximate prevalence of 1 in 700,000 individuals.¹ Most evidence of PRS derives from case reports rather than large studies. This means that it is difficult to fully comprehend the disease or to generate standardised treatment guidelines. This article will discuss the ophthalmologic manifestations in patients with PRS as well as management options to reduce exacerbated symptoms. 

Overview of ophthalmologic involvement and pathophysiology 

Ocular manifestations occur in 10%-35% of patients with PRS, which can occur before, during, or even after facial atrophy.² The exact mechanism behind PRS remains elusive, which is probably due to its rarity; however, a few theories have been suggested:

Autoimmune process

Several scientists and researchers predominantly consider PRS as an autoimmune disease.³ Evidence to support this derives from the presence of autoantibodies, which are proteins released by the immune system that mistakenly attack the body’s own healthy cells and tissues.³ An improvement in lesions following immunosuppressive treatment and Inflammation in tissue biopsies also strongly suggest an immune-mediated process. 

Neurogenic theory 

Another theory is the involvement of the trigeminal nerve.⁴ This nerve provides sensation to your face as well as motor control to your jaws, such as chewing. It is possible that inflammation or abnormality of this nerve causes a breakdown of tissue in the face.^{4, 5} Moreover, the trigeminal nerve is also close to some brain pathways, which could explain neurological malformations in PRS, such as seizures. If the ophthalmic branch of the trigeminal nerve is affected, it may reduce the sensation in the cornea, which can cause damage to vision.^4,5 

Due to underlying autoimmune and neurogenic mechanisms, patients often present with eye complications such as enophthalmos (sunken eyes), uveitis, ptosis (droopy eyelid), and corneal involvement. 

Specific ophthalmologic complications 

Enophthalmos (sunken eyes)

Enophthalmos is one possible complication of PRS, where the clinical appearance is a sunken eye. This occurs due to the atrophy of fat and tissue surrounding the eye, causing the eye to appear hollow on the affected side of the face.⁶ 

Ptosis (weak eyelid muscles)

Ptosis is where the muscles in the eyelid start to degenerate and become weak and are unable to hold the eyelid up.⁷ As the eyelid droops, patients have complained of decreased and sometimes even complete occlusion of vision.⁷ 

Corneal involvement 

The cornea is the outer layer of the eye, which is transparent and acts as a “shield” to protect the eye. In PRS, corneal involvement, also known as “keratopathy”, is infrequent but can still cause damage to vision.⁷ This occurs due to the eyelid not closing properly, as well as facial nerve involvement, which overall decreases sensation in the cornea. 

Uveitis 

Another ophthalmologic complication of PRS is uveitis, which is inflammation inside the eye. Clinical features of uveitis include red eyes, pain, and blurry vision.⁸ Currently, there are 23 cases of uveitis associated with PRS reported in literature.⁹ Despite this small number, the consequences of uveitis can be quite large for patients with PRS. Chronic uveitis can result in a feared complication termed "hypotony".  This is where the pressure inside the eye drops abnormally low and can pose a threat to vision. It can also cause glaucoma and cataracts.^9,10 

Diagnosis and monitoring 

PRS is a condition that affects each patient differently, so regular and comprehensive eye checks are crucial. Making an initial diagnosis of PRS can prove challenging and typically takes several years.³ It has to include the medical history of the patient, examinations, and elimination of other causes. Imaging techniques and histopathology may also be used to help in forming a diagnosis.³ A diagnosis can consist of the following: 

Clinical examination

Clinical examination includes:⁹

• Facial examination: Ophthalmologists will first have to examine the face and the eye socket for any indication of enophthalmos, ptosis, or asymmetry between the two sides of the face
• Eyelid examination: To check if the eyelids fully close, because if there is partial closure, this could predispose to exposure keratopathy 
• Corneal health: Slit-lamp exam can detect dryness, ulcers, and scarring of the cornea (trigeminal nerve involvement) 

Vision testing

Vision testing includes:³ 

• Visual acuity: Snellen chart test to measure the sharpness of vision. Significant changes can indicate uveitis
• Colour vision testing: Slight optic or retinal nerve damage can be identified by reduced colour differentiation, which often happens before vision loss
• Visual fields: Perimetry can be utilised to detect blind spots, which may occur with optic nerve damage or retinal involvement

Neuroimaging

PRS also affects the nervous system, so it is important to scan for any neurological malformations.¹¹ 

• CT scans can detect fat loss of the eye socket, structural changes to the bone, and asymmetry of the eye socket 
• MRI scans can show us changes to soft tissue and the brain, such as seizures or abnormalities to the trigeminal nerve 

Monitoring 

Although PRS typically stabilises after a couple of years, eye complications can persist and may progress. Patients with PRS should continue to receive support and care from an array of medical professionals; they should coordinate with each other to ensure nothing is missed. Further, children are especially vulnerable, as the development of their vision may be affected permanently. Adults also require long-term monitoring for a late onset of uveitis or retinal changes. 

Treatment and management

Unfortunately, there is currently no cure for PRS.² Therefore, the aim of management is to prevent the active progression of the disease and induce remission, treat complex exacerbations such as uveitis, and provide cosmetic rehabilitation after complete remission.   

Patients with ophthalmologic malformations in PRS should have access to efficient general and supportive care that includes artificial tears or lubricating eye drops to reduce dryness in the eye. Moreover, protective eyewear such as eye shields or goggles for patients who have poor eyelid closure.² 

In acute uveitis, relapses are quite common, and so aggressive management is typical. Treatment is mainly utilised to reduce the level of inflammation in the eye as well as alleviate pain. Medications often used are cycloplegic drugs, which are administered to the eye in the form of eye drops to reduce pain by temporarily paralysing the ciliary muscle in the eye.² Topical steroids are also standard for uveitis and aid in the reduction of inflammation, but have to be used under the close supervision of an ophthalmologist due to the potential risk of increased eye pressure and development of cataracts.² 

Surgical treatments are also available for cosmetic and medical purposes. For example, intraorbital injection of filler such as silicone gel can be used for enophthalmos to reduce the hollow and sunken appearance of the eye. Plastic surgeries such as skeletal reconstruction and tissue transplantation are also treatments but have varying success rates.¹² 

Overall, as PRS can have a multitude of malformations, such as eyes, skin, neurological, and mental, a multidisciplinary approach is vital. Various doctors from different specialities should be involved in the care of PRS patients, ensuring that both physical and mental health needs are met. 

Summary 

Parry-Romberg syndrome (PRS) is a rare and complex disorder that can progress from the skin to as deep as the bone. Although the ophthalmologic malformations in PRS are frightening and can be sight-threatening, fully understanding and managing the disease is hindered by the extreme rarity of the condition. Currently, knowledge on PRS comes from case reports, which makes it challenging to generalise findings. To identify problems early and direct treatment, PRS needs eye and neurological monitoring, including clinical examinations, vision tests, and imaging.  Although there is no known cure, treatment focuses on managing the disease's development, treating acute conditions like uveitis, and offering supportive measures like lubricating eye drops, protective eyewear, and topical drugs under expert supervision as needed. Further research should be conducted on PRS using larger studies to clarify the mechanism of the disease so that improvements can be made to diagnosis and treatments.