Giant Fornix Syndrome

Etiology

The precise etiology is unknown. The original study by Rose postulated that extraordinarily deep fornices, probably caused by age-related levator aponeurosis degradation, provide a favorable environment for bacteria to reside. Mild conjunctivitis, possibly exacerbated by blocked lacrimal ducts, could cause an increased bioburden in the superior (and more rarely, inferior) conjunctival fornices. The toxicity of this bioburden leads to increased protein-based exudate from the inflamed conjunctiva. These events will create a positive feedback loop in which the exudate protects the bacteria, the bacterial bioburden increases and causes inflammation of the conjunctiva, which causes more protein exudation.[6] The exudate likely protects the bacteria from topical and systemic antibiotic treatment, leading to recurrent infections without resolution.

Epidemiology

In the Rose study, '''patients' age ranged from 77 to 93 years old, with a mean of 86 years. Women appear to have a higher risk of developing giant fornix syndrome, with a ratio of ten females to 2 males reported. In another study, the ratio was six females to 2 males affected, with ages ranging from 76 to 89 and a mean of 82 years.[5] Other case studies indicate the mean age is typically in the seventh to the eighth decade.[2][3][4]

There is no extensive population data on this disease due to the rarity and misdiagnosis. The condition is usually limited unilaterally, but some cases occur bilaterally.[5] Occasional recurrences after the initial resolution have been reported, but these recurrences may be due to the inadequacy of treatment. Cases have been reported in Asian and Caucasian populations, but additional studies in other demographic groups are needed to determine if race plays a role in GFS risk factors. There is one case of a patient who was only 33 years old but had extensive trauma and surgical intervention.

Pathophysiology

Staphylococcus aureus is the primary bacteria cited in giant fornix syndrome, but Pseudomonas aeruginosa and Serratia marcescens have also been isolated.[6][7] A Pseudomonas aeruginosa and methicillin-resistant Staphylococcus aureus polymicrobial infection was noted in one case.[2]

Histopathology

Positive cultures of the purulent discharge have primarily shown S. aureus infections, but P. aeruginosa and S. marcescens are also noted in several studies.[6][7] A patient diagnosed with giant fornix syndrome had a conjunctival biopsy sent for evaluation.[8] The biopsy revealed a mix of B and T cells after immunohistology staining indicating persistent infection.

History and Physical

The primary signs and symptoms of giant fornix syndrome are chronic conjunctivitis with abundant, yellow purulent discharge and abnormally deep superior (or rarely inferior) conjunctival fornices. Some associated symptoms may include but are not limited to redness, pain, blurry vision, ptosis, and foreign body sensation.

Giant fornix syndrome is typically unilateral but can be bilateral. Patients may present with ptosis due to underlying inflammation of the superior conjunctiva. In severe cases, patients misdiagnosed for months to years may have corneal damage, including scarring, near or complete corneal perforation, vision impairment, pseudomembranous formation, and punctate epithelial keratopathy.[6]

Evaluation

CT scans have shown what appears to be pockets of air located in the deep superior conjunctival fornices. Authors have postulated that this may be another sign of giant fornix syndrome. CT can also rule out foreign bodies and frontal sinusitis.[9] In another patient, free air in the superior conjunctival space was present, but the patient had no complaints of eye pain, no evidence of conjunctivitis, and no other indications for GFS other than deep fornices. While this patient may be more prone to GFS, there was no physical exam-based evidence to diagnose her with GFS. In this case, there is further evidence that CT may help diagnose giant fornix syndrome but should not be considered the definitive test for GFS. Relevant physical exam findings corroborated by free air on CT would provide strong evidence for GFS diagnosis.[10]

Treatment / Management

Several potential treatment courses have been tried with varying success ranging from the non-invasive application of antibiotics and high dose steroids to surgical interventions.

Current options for treatment include:

• Systemic antibiotics
• Topical antibiotics
• Topical steroids
• Dilute antiseptic washes/swabs
• Manual swabbing to reduce bacterial load
• Subconjunctival Antibiotic Injections
• Antimicrobial solution rinse
• Autologous serum eye drops
• Hypochlorous acid treatment of eyelashes
• Surgical resection

In the first retrospective study describing the existence of an unknown disease, now defined as GFS, twelve patients were treated with various systemic, high dose topical antibiotics and high dose topical steroids. All 12 saw a marked reduction in symptoms. Eight of the twelve needed daily treatment with topical combined antibiotic/steroid eye drops to avoid recurrence of symptoms. The remaining four saw the complete resolution of most GFS-related symptoms. Several had persistent ptosis, but the severity lessened after treatment of the underlying disease.[6](B3)

In a 97-year-old female, sweeping the superior conjunctival fornices with a cotton swab soaked in 10% povidone-iodine was noted to cure giant fornix syndrome after several attempts at medical treatment failed to stop a relapse. Her initial six-month treatment regimen of topical polymyxin–trimethoprim eyedrops and several fluoroquinolone eyedrops removed P. aeruginosa from her eye but could not clear the remaining MRSA infection. The treatment was switched to a tobramycin and vancomycin eyedrop regimen with worsening symptoms. The patient was unable to tolerate systemic antibiotics. The drug regimen was shifted to a combined vancomycin and prednisone eye drops, including subconjunctival injections of vancomycin and triamcinolone, which led to marked improvement. However, after another relapse, more aggressive treatment with 10% Povidone-Iodine forniceal swab was completed six times within ten days. She was considered clinically cured and remained infection-free while in contact with the clinic.[2](B3)

Several surgical resection techniques have been used to reduce the depth of the superior fornices and close the large space harboring bacteria. One retrospective case series involved the resection of the superior and inferior conjunctiva ranging from 4-10mm (subjective, estimated by the surgeon) along with subconjunctival antibiotic injections and electrocautery of the conjunctival bed resulted in positive outcomes. Within one week, several symptoms, including redness, conjunctival injection, purulent discharge, and corneal punctate epitheliopathy, saw marked improvement on physical examination. Complete resolution of most symptoms occurred within three months, and no recurrent infections were reported within nine months.[4] Another study with a similar surgical procedure on six patients reported a partial reduction in symptoms in 2 patients and a complete reduction in symptoms in 4 patients over a more extended observation period. The superior conjunctiva was resected by 6 to 10 mm (measured formally). This study differed primarily because the authors did not resect the inferior conjunctiva unless a pseudomembrane was discovered on physical examination.[11](B2)

Another retrospective study compared the depth of resection to surgical outcomes. Ten patients were assigned to the "limited" or "maximal "resection group based on their reduction during Müller's muscle conjunctival resection (MMCR) procedures. Limited MMCR was defined as 6 to 8 mm, and maximal MMCR was defined as 10 to 12 mm resection. Results indicated that maximal MMCR was more successful than limited MMCR. Maximal MMCR led to complete symptom reduction without any additional surgeries within an average of 2.06 months. All three limited MMCR patients required additional resections to resolve their symptoms. These data suggest that more extensive resections correlate with better procedure outcomes. The authors did not suggest an upper limit to resection. They expressed concern over the upper lid and lacrimal gland function impairment, but none of the ten patients had observable or reported problems with post-operative tear production.[5]

Differential Diagnosis

Like giant fornix syndrome, many ocular diseases present with chronic conjunctivitis, which may delay the correct diagnosis. Causes of chronic conjunctivitis with similar presentation include but are not limited to:

• Ocular allergies
• Dry eye
• Blepharitis
• Scleritis
• Dacryocystitis (also typically involves S. aureus)
• Canaliculitis
• Nasolacrimal duct obstruction
• Lacrimal sac mucocele

Ocular allergies may be less likely if the patient does not have other chronic allergies such as asthma or eczema. While severe cases of ocular allergies may persist, most would respond to the use of antihistamines.[12] Lack of response may rule out allergies, and a bacterial culture swab is advised. 

If a positive culture with a large bioburden is obtained, giant fornix syndrome and dacryocystitis should be considered. Dacryocystitis may be ruled out if patients continue to have symptoms despite patent lacrimal ducts after a successful lacrimal surgery. If the treatment regimen for chronic dacryocystitis does not yield results, the patient may be assessed for GFS risk factors.[3]

Prognosis

This disease is recurrent, chronic, and difficult to treat. The prognosis depends on early diagnosis and the response to treatment. If allowed to run its course without intervention, this disease may, in severe cases, cause corneal perforations and ulcers. A detailed history and physical exam will be the key to diagnosis. CT scans may assist in diagnosing but should not be used to rule out giant fornix syndrome.[9][8] Surgical intervention could be considered for severe cases, as they have the shortest recovery time and the highest symptom resolution rate. If the symptoms are milder, less invasive techniques could be considered to limit the risk of surgical side effects.

Mild disease appears to be effectively curable within weeks if treated with systemic antibiotics and high dose antibiotic/steroid combination eye drops. Mild to moderate disease can also be treated similarly but may require life-long use of a low dose antibiotic/steroid combination eye drop to prevent reoccurrence. Mild, moderate, and possibly severe disease can potentially be treated or cured in weeks with aggressive use of povidone-iodine washes and manual disruption of the coagulum using a cotton swab in conjunction with antibiotics and steroids.[2] Surgical resection ranging from 8-12 mm of the superior conjunctiva supported by dilute antiseptic and antibiotic/steroid combinations appears to have the highest efficacy. Data from all studies cited indicate a very high success rate with surgical procedures and a low risk of side effects.[11][5][4]

Complications

Severe disease can result in a corneal ulcer and perforation of the cornea. Non-traumatic perforation of the cornea has a lower success rate for repair. Unrepaired perforations of the cornea can lead to irreversible glaucoma, endophthalmitis, and blindness.[13]