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January 08, 2021
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Young woman presents with conjunctival lesion of right eye

The patient recently underwent an eyelash procedure while wearing contact lenses.

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A 26-year-old woman was referred to the Lahey Clinic for evaluation of a recurrent conjunctival lesion of the right eye.

The patient reported having an eyelash tint and lift procedure a week prior while wearing her contact lenses. She believed that the adhesive used during the procedure got onto her right eye as she felt irritation and noticed a white spot overlying the sclera the following day. She also had associated aching pain and intermittent blurry vision. She tried over-the-counter artificial tears and gel drops at bedtime, but her eye continued to feel irritated and dry. She did not wear her contact lenses following the eyelash procedure. The patient was initially evaluated by an outside ophthalmologist who removed some foreign material thought to be eyelash adhesive from the surface of the right eye; however, the lesion returned upon follow-up 10 days later.

Christine Benador-Shen
Christine Benador-Shen
Malgorzata Dymerska Peterson
Malgorzata Dymerska Peterson

The patient’s medical history included GERD, depression and anxiety. She had no previous surgeries. Her medications included citalopram daily and lorazepam as needed for anxiety. She had no known drug allergies. She had no history of cigarette smoking or drug use and reported only social alcohol drinking. There was no known ocular disease in the family. A review of systems was otherwise negative.

Examination

The patient’s corrected visual acuity with glasses was 20/20-1 in the right eye and 20/20 in the left eye. The pupils were round and reactive bilaterally with no afferent pupillary defect. IOP was within normal limits bilaterally. Extraocular eye movements and confrontational visual fields were full bilaterally.

On external exam, the patient had mild right upper lid edema and ptosis. Slit lamp examination was notable for an elevated white, waxy lesion at the temporal bulbar conjunctiva at 10 o’clock in the right eye (Figure 1a) with focal mild injection of the conjunctiva. There was no associated neovascularization or pigmentation. The lids were everted and fornices were examined with no residual foreign body identified in the right eye. There were 2+ papillae of the superior and inferior palpebral conjunctiva in the right eye. There were no foreign bodies noted in the left eye. There were 1+ papillae of the superior and inferior palpebral conjunctiva in the left eye. Other aspects of the anterior segment examination, including the cornea, anterior chamber, iris and lens, were otherwise unremarkable bilaterally.

Slit lamp examination
Figure 1. Slit lamp examination of the conjunctiva in the right eye demonstrating a mildly elevated white, waxy lesion at the 10 o’clock position with mild associated injection. Lesion before initial removal at the office (a). Recurrence of the lesion approximately 3 weeks later (b).

Source: Yi Ling Dai, MD, Naveen Rao, MD, and Nora M.V. Laver, MD

What is your diagnosis?

See answer below.

Conjunctival lesion

The differential diagnosis for a conjunctival lesion ranges from benign to malignant causes.

Conjunctival granuloma as a reaction to a foreign body (in this case, the eyelash adhesive) was a likely diagnosis as it often presents as a pink nodular elevated lesion in the absence of obvious conjunctivitis. Conjunctival papilloma is the most common benign neoplasm of the conjunctiva and often presents as a finger-like and/or cauliflower-like lesion with central vascular cores, which was not the appearance of this patient’s lesion. Pinguecula is a common benign conjunctival lesion that is most commonly found at the nasal conjunctiva. Although this patient’s lesion appeared similar to a pinguecula, it is not usually located superotemporally in an area not exposed to the sun. A Bitot’s spot, which is associated with vitamin A deficiency, presents as a dirty white or silvery gray patch with a foamy appearance and is often bilateral. Conjunctival keratotic plaques are premalignant white conjunctival masses with keratinized epithelium. Conjunctival intraepithelial neoplasms and invasive cancers of the conjunctiva were also on the differential, although less likely given our patient was a young adult.

Additional workup

The white foreign body was subsequently scraped off with jeweler’s forceps and moist cotton tips. Ofloxacin, prednisolone and erythromycin were applied after the procedure. The patient was started on prednisolone eye drops four times a day for possible unusual inflammatory reaction to the eyelash glue causing hyperkeratinization. However, the patient continued to complain of irritation and recurrence of the white foreign body despite repeated attempted removal during subsequent visits (a total of three attempts; Figure 1b). Anterior segment OCT of the lesion revealed a thickened and hyperreflective epithelial layer with an abrupt transition from normal to abnormal epithelium (Figure 2).

AS-OCT
Figure 2. AS-OCT of the hyperreflective, thickened conjunctival lesion (asterisk). The dotted line indicates the inferior border of the conjunctival epithelium. The red arrow denotes the abrupt transition from normal to abnormal tissue.

During the patient’s third visit, the white waxy material was scraped off, transferred to a slide and sent for pathological analysis, which confirmed that the lesion was made of keratin and not foreign material. Bacterial and fungal cultures of the lesion were negative. Given the AS-OCT appearance and pathology results, there was high suspicion for ocular surface squamous neoplasia (OSSN). The patient subsequently underwent conjunctival excisional biopsy with amniotic membrane transplantation. Tissue pathology analysis revealed conjunctival intraepithelial neoplasia 1 without evidence of malignancy (Figure 3).

Pathological slide
Figure 3. Pathological slide showing keratinizing squamous neoplasia of the excised conjunctival mucosal tissue. Red circle denotes abnormal proliferating basal cells. Red arrow denotes squamous cells. Red asterisk and bracket denote surface keratin.

Of note, the patient received the HPV vaccine at the age of 12 years and had a normal Pap smear 1 year before presentation. The patient admitted to frequent tanning using tanning beds but claimed that she always wore the supplied goggles during tanning sessions.

Discussion

Conjunctival intraepithelial neoplasia describes neoplasia of squamous cells that are confined to the conjunctival epithelium with no evidence of invasion into the substantia propria. It falls under the umbrella term of OSSN, which ranges from mild dysplasia to invasive carcinomas. This includes squamous papillomas, conjunctival-corneal intraepithelial neoplasia, carcinoma in situ and invasive squamous cell carcinoma.

The incidence of OSSN is relatively low at 0.13 to 1.9 cases per 100,000 and most commonly occurs in men between the ages of 50 and 75 years old. The most well-documented risk factors for the development of OSSN are sun exposure (more specifically, ultraviolet B) and infection with HPV. Other known risk factors include a propensity to sunburn, fair skin, pale irises, xeroderma pigmentosum, history of skin cancers, trachoma, chronic irritants (eg, contact lens use) and vitamin A deficiency. Immunosuppression is an important risk factor for OSSN, and positive HIV status can increase the risk for conjunctival malignancies 13-fold. OSSN in younger patients may indicate underlying immunodeficiency; a study by Karp and colleagues showed 50% of patients with OSSN younger than 50 years old had HIV. HIV status is also associated with a more aggressive course of OSSN.

As OSSN often occurs in readily visible areas, detection of the disease is typically early. Patients often present with chronic eye irritation, red eye and tearing but can also be asymptomatic. Lesions vary widely in appearance but often appear as a fleshy elevated mass at the limbus in the interpalpebral zone. They may or may not have prominent feeder vessels and may initially appear mobile.

Diagnosis is often clinical, based on slit lamp biomicroscopy and confirmed with tissue pathology. As there is potential for malignant seeding, excisional biopsy of these lesions is preferred over incisional biopsy. Histopathological studies show epithelial hyperplasia with loss of goblet cells and cell polarity, nuclear hyperchromasia and pleomorphism and evidence of cell mitosis. There can also be surface keratinization.

Management of OSSN lesions is geared toward total eradication and can be achieved through a combination of methods, depending on disease severity. Large margins (2 mm to 4 mm) are used during surgical removal; in cases of large wound defect, an amniotic membrane or autoconjunctival graft may be used for wound closure. Topical chemotherapy (eg, interferon alpha-2b, mitomycin C, 5-fluorouracil) can be used for primary treatment or in conjunction with surgical excision (eg, in the case of positive margins). The recurrence rate of OSSN nowadays ranges from 5% to 15%. Factors associated with higher recurrence rates include positive surgical margins, involvement of more than 50% of limbal stem cells and tarsal tumor location.

Our case was especially atypical as it presented in a young healthy patient who was adamant that the lesion appeared after foreign body exposure (eyelash glue). In a retrospective study by Dandala and colleagues, there was a significant association between young age at the time of presentation with OSSN lesions and HIV status. The study deemed HIV testing necessary in any young patients with OSSN. Our patient denied any risk factors for HIV but was nonetheless recommended to obtain HIV testing, the results of which are pending at this time.

Our patient’s presentation also raises a question of acute inflammation triggered by foreign body exposure causing metaplasia and/or dysplasia, leading to conjunctival intraepithelial neoplasia. Chronic inflammation is an established predisposing factor in metaplastic and dysplastic changes. In a case series by Theotoka and colleagues, a number of patients with corneal scarring in the setting of chronic inflammatory conditions (eg, ocular rosacea, HSV keratitis and Acanthamoeba keratitis) were ultimately diagnosed with OSSN. However, there is no known association between acute inflammation and OSSN development thus far. While it is a possibility, it may just be that the patient already had OSSN, and the foreign body exposure was simply a coincidence that led to its discovery.