Corneal hypersensitivity associated with blepharokeratoconjunctivitis in a post-partum female adult

A Case Report

Corneal hypersensitivity associated with blepharokeratoconjunctivitis in a post-partum female adult

Nicole Sehn BHSc OD Candidate 2017
Nicole Sehn BHSc OD Candidate 2017

Background: Blepharokeratoconjunctivitis is a chronic inflammatory disease of the palpebral margin with secondary corneal and conjunctival involvement.The corneal damage results from an immune reaction instigated by bacteria situated along the lid margins and distributed across the ocular surface during blinks. Along with disruption of the meibomian gland secretions, the ocular surface is more susceptible to medicamentosa.

Case History: A 38-year-old post-partum female presented with concerns of increased tearing and mucous debris along the lashes of both her eyes. She had been using Visine to resolve her symptoms. Examination of the anterior segment for both eyes revealed staphylococcal blepharitis, capped meibomian glands, evident grade 4 papillae on the superior and inferior palpebral conjunctiva and a diffuse grade 4 superficial punctate keratitis. Management consisted of lid hygiene, lubrication and a steroid-antibiotic therapeutic to resolve the ocular surface inflammation and bacterial overgrowth. The blepharitis improved remarkably well; however, the corneal and conjunctival irritation remained after two weeks of treatment.

Conclusion:Multiple factors including blepharitis, rosacea, allergies, and hormone fluctuations, can disrupt the tear film’s integrity leading to dry eye syndrome. With a lack of high quality tears, the ocular surface is more susceptible to irritation or toxicity from external sources such as medications. This case demonstrates the importance of consciously selecting preservative-free therapeutics to efficiently resolve inflammation associated with dry eye and hypersensitivity reactions.


Key Words: blepharokeratoconjunctivitis, dry eye, meibomianitis, toxic conjunctivitis


Introduction

Toxic keratoconjunctivitis results from chronic exposure to a foreign chemical such as a preservative or a combination of medications on the ocular surface1,2. The process commonly involves a Type IV hypersensitivity reaction, which is an immune reaction initiated towards an allergic or immunogenic agent1. Symptoms commonly include pain, hyperemia, chemosis, puritus, superficial punctate keratitis (SPK) and papillae or follicles in the palpebral conjunctiva1,2. This paper reports a moderate case of unresolving medicamentosa aggravated by concurrent ocular surface disease related to inflammation of the meibomian glands.

 

Case Report

A 38-year-old Native American female on maternity leave for approximately 7 months presented to our clinic to address an ongoing ocular concern. Her chief complaint was an increase in tearing and crusts on the inner corners of her eyelids and along her lashes. The amount of mucous was noticeable enough that it needed to be removed frequently throughout the day. The onset of her symptoms were not clarified but remained stable for the past two weeks. She denied any pain, redness and itching.

Previous ocular findings were unavailable as her last eye exam was 10 years ago at a different clinic, but the patient confirmed that she had not been diagnosed with any ocular conditions.In addition, she had not experienced any concerns with her vision during that period of time. There was no history of trauma, infection, inflammation or surgery to her eyes. The patient did not notice any visual changes during pregnancy and post-partum. She also confirmed that she had not been diagnosed with any systemic conditions and her family history was unremarkable for any medical or ocular conditions. The sole medication she had been using was Visine to manage her ocular symptoms.

Pertinent examination findings are listed in Table 1 (see appendix). Unaided visual acuities were 6/6-2 OD and 6/6 OS. Slit lamp examination revealed debris at the base of the lashes, an accumulation of makeup along the eyelashes and lid margins and capped meibomian glands OU. Both eyes had a high tear prism along with diffuse Grade 4 SPK and Grade 4 papillae on the superior and inferior palpebral conjunctiva. Three subepithelial sterile infiltrates adjacent to the inferior and superior nasal limbus were observed OS. Although the patient was highly photosensitive, no anterior chamber reaction was identified. An undilated view of the posterior segment was observed and found to be within normal limits.

Patient education and management included discontinuation of Visine as well as a breakfrom wearing make-up until the ocular irritation resolved. Tobradex was prescribed (bid x 7days) along with Systane lid wipes (qd), hot compresses (bid x 10min) and non-preserved artificial tears (BION tears, qid). The patient returned after one week of treatment for follow-up care. It was found that the patient’s ocular comfort had noticeably improved and she was exceptionally compliant to the therapeutic regimen. There were no signs of mucous discharge, lash debris or makeup and the capped meibomian glands were now patent. The patient also reported the tearing had returned back to normal levels. However, irritation to the superior and inferior palpebral conjunctiva and cornea were still evident, and both were recorded as a Grade 3 reaction. The three subepithelial infiltrates OS remainedunchanged. The medication was adjusted to exchanging Tobradex for tobramycin, while maintaining the other treatment components.

At her second follow-up appointment, one week from the previous visit, the patient’s ocular signs were still unresolved. The diffuse SPK and papillae had minimally reduced to a Grade 2 response and the subepithelial infiltrates OS were still noted. At this point, the patient’s daily routine and systemic health were re-evaluated to confirm any associations for her unresolving ocular inflammation. The patient denied the use of sprays (i.e. hair) or working with aerosols, allergies to make-up, and rubbing creams near her eyelids. This eliminated common sources for evaporative dry eye. The patient’s responses were also negative for previous diseases, auto-immune conditions, health concerns (i.e. blood work was recently normal), complications during pregnancy, hormonal fluctuations postpartum, and skin-related sensitivities. This eliminated common etiologies for aqueous deficient dry eye.

A non-urgent referral to a corneal specialist was initiated and her management was followed for two appointments. Results from the ophthalmology consults are outlined in Table 2 (see appendix). The last recorded treatment was Flarex taper, azithromycin (1g x 1) and Patanol (bid OU).

 

Discussion

Tear film stability is a primary factor in maintaining the physical properties and functionality of the anterior ocular structures3. Alteration to the osmolarity or composition of the tear film disrupts the sensory balance interconnecting the lacrimal gland and ocular surface3,4. Ultimately, the performance of the lacrimal functional unit is compromised reducing the quantity and quality of tears. This alters the cornea’s protective ability because a lowered tear film decreases drug dilution, through non-specific binding5. Consequently, the drug’s contact time with the cornea is increased promoting further absorption and subsequent effects5. Similarly, our patient had multiple factors disrupting her tear film that increased susceptibility to toxic keratoconjunctivitis.

First, our patient presented post-partum suggesting prior risk to experiencing pregnancy related dry eye syndrome. Studies have shown that expecting females are more prone to keratoconjunctivitis sicca, with symptoms even throughout nursing due to hormonal changes6. Receptors for androgens, estrogen and progesterone have been identified on the ocular surface, lacrimal and accessory glands as well as meibomian glands indicating hormone levels regulate their function6. The loss of androgens reduces the quality and quantity of lipid in meibum whereas estrogen and progesterone genetically suppress sebaceous glands6. Androgens have also been observed to promote lacrimal gland secretions6. Yet, further research is needed for the role of estrogen and progesterone on the lacrimal gland6.

Next, the proposed patient diagnosis had an integral relationship with ocular surface disease as it influences the integrity of meibomian gland function. Meibomian glands are commonly linked to evaporative dry eye due to a reduction in lipid secretion7.

However, these glands can also become inflamed resulting in three additional conditions such as ocular rosacea, phlyctenular keratitis and blepharokeratoconjunctivitis (BKC) 7. BKC is a chronic bilateral inflammatory disease involving the palpebral margin with secondary conjunctival and corneal complications8. It can present in adults and children, and is most commonly in females7,8. BKC is caused by anterior blepharitis that induces meibomitis from bacterial overgrowth7. Lipolytic enzymes produced from the bacteria alter meibum production7. Abnormal lipid secretions deposit into the tear film and reduce the integrity of the corneal epithelium7. Since the palpebral margins are dynamic, they rub along the surface during blinks spreading irritation7.

Proper diagnosis of BKC is crucial to prevent severe corneal damage that can compromise vision7,9. BKC will present with acute signs such as inflamed eyelids, telangiectasia, collarettes at the base of cilia, inferior SPK and sterile infiltrates8. The corneal inflammation will also induce reflex tearing, itching, foreign body sensation, burning and photophobia10. As BKC progresses, it can lead to more severe signs like madarosis, trichiasis, lid notching, ulceration, papillae/follicles on the palpebral conjunctiva, corneal scaring and corneal neovascularization8.

The recommended treatment for BKC is directed towards eliminating bacteria on the lid margins and resolving the inflammatory reaction obstructing the meibomian glands10. Expression of the meibomian glands is restored through repeated hot compresses and lid margin cleaning10. Topical antimicrobials are prescribed to cleanse the lid margin and conjunctiva from bacteria10. In order to resolve the ocular surface inflammation, topical immunosuppressants and lubricants are used to reduce and dilute the inflammatory mediators in the tear film10. Medications combining steroids with antibiotics such as loteprednol etabonate 0.5%/tobramycin 0.3% and dexamethasone 0.1%/tobramycin 0.3% (1-2gt qid, 14days) have both shown equal efficacy in decreasing the ocular inflammation associated with BKC11. In contrast, antibiotic-only agents such as tetracycline and macrolide are also competitive alternatives to steroid combination therapies since they can provide anti-inflammatory properties as well10. Both tetracyclines and macrolides can penetrate the ocular tissues, including meibomian glands, and remain at therapeutic levels days after therapy has stopped12.

Although this ophthalmic therapy is recommended, it’s important to recognize our patient had already been treating her symptoms with Visine (tetrahydrozoline 0.05%). Moreover, due to the previous factors altering her tear film, it is likely that Visine aggravated a diffuse adverse toxic reaction. Topical decongestants can produce acute and chronic forms of conjunctivitis through toxic mechanisms13. Visine contains the preservative benzalkonium chloride (BAK), which is frequently related to hypersensitivity side effects14. It has a high potential to cause severe reactions since it accumulates and remains in the tissue for long periods increasing the overall concentration14. BAK interferes with cell layer continuity, which is seen clinically as SPK14. The epithelium becomes more permeable causing the process to repeat and progressively worsen14. The lipid and mucin components are also disrupted leading to dry eye14.

In cases diagnosed with toxic keratoconjunctivitis, the primary treatment is to remove the offending agent1. Discontinuing the use of as many topical medications, including lid wipes, supports successful therapy in hypersensitivity conditions1. If supplemental medication is required, a preservative-free preparation should be used1. It is recommended, to use preservative-free artificial tears or steroid ointments to control and reduce surface irritation. In our case, this management was not followed due to concerns of infection. However, after several follow-up visits and ophthalmology consults, the condition was unresolving. It is suspected based on the patient’s poor quality tear film, primarily caused from BKC, that the use of multiple topical medications prolonged the corneal and conjunctival hypersensitivity. In effect, the  inflammatory response manifested as bulbar conjunctival papillae/follicles, marginal infiltrates and SPK could not resolve.

In retrospect, the outcome of our patient could have been more successful considering this case as a unique and holistic entity versus a typical presentation of BKC. It is standard of care to follow the treatment guidelines for a particular diagnosis; however, our patient involved additional factors such as post-partum hormonal fluctuations and toxic keratoconjunctivitis that complicated the healing process on the ocular surface. We prescribe medications with the intent to solve a patient’s problems, but we should also predict how they could negatively impact their recovery. If the treatment is not effective, it is the practitioner’s responsibility to consider alternate options.

 

Conclusion

The dynamic interaction between the tear film, cornea and conjunctiva is demonstrated by BKC. Numerous factors such as debris accumulation and bacterial overgrowth can obstruct the meibomian glands7. Subsequent deposition of pathogen-related byproducts and reduction of lipid secretions from meibomianitis significantly alters tear film quality7. A lack of proper tear film components exposes the vulnerable ocular surface to damage, especially from toxicity to topical ophthalmic medications and their preservatives3,5,14. Both pathologies complicate the method of treatment as prescribing drugs could resolve the infection but prolong the hypersensitive-induced inflammatory reaction. All things considered, it is imperative that the ocular inflammation is addressed in order to prevent further visual impairment.

 

Acknowledgements

The author would like to thank Dr. A. Weinerman for her clinical supervision during this case and Dr. S. Maciver for providing literary guidance to identify the proposed pathological process of my patient.

 

Appendix

OD Examination Results OS
Appointment 1:
6/6-2 Unaided VA (Distance) 6/6
Non Strab- Ortho Cover Test Non Strab- Ortho
Smooth/Equal/Accurate EOM Smooth/Equal/Accurate
FTFC VF FTFC
PERRL/(-)RAPD Pupils PERRL/(-)RAPD
12mmHg IOP (NCT @10:58am) UTA
Lash debris/ lots of makeup/ capped meibomian glands Lids Lash debris/ lots of makeup/ capped meibomian glands
Epidermal Cyst (inferior temporal and superior nasal); High tear prism Bulbar Conjunctiva High tear prism
Flat and Intact Iris Flat and Intact
Photosensitive- no cells and flare Anterior Chamber Photosensitive- no cells and flare
Diffuse SPK Grade 4 Cornea Diffuse SPK Grade 4; Subepithelial sterile infiltrate (3)
Papillae Grade 4 Palpebral Conjunctiva Papillae Grade 4
Appointment 2:
Clear Lids Clear
Clear Bulbar Conjunctiva Clear
Less photosensitive Anterior Chamber Less photosensitive
Diffuse SPK Grade 3 Cornea Diffuse SPK Grade 3; Subepithelial sterile infiltrate (3)
Papillae Grade 3 Palpebral Conjunctiva Papillae Grade 3
15mmHg IOP (NCT) 10/16mmHg
Appointment 3:
6/7.5+2 Unaided VA (distance) 6/7.5+2
Diffuse SPK Grade 2 Cornea Diffuse SPK Grade 2
Papillae Grade 2 Palpebral Conjunctiva Papillae Grade 2
12.5mmHg IOP (NCT @11:34am) 11.5mmHg

Table 1. Examination Findings from the Ocular Assessments.

 

OD Examination Results OS
Appointment 1:
6/12+1 Unaided VA (Distance) 6/9-1
Central SPK Cornea

Central SPK;

Superior Corneal Neovascularization

Mixed Follicles and Papillae Palpebral Conjunctival Mixed Follicles and Papillae
12 IOP (@ 9:43am) 16
Appointment 2:
6/7.5-1 Unaided VA (Distance) 6/7.5
Central SPK Cornea

Central SPK;

Superior Corneal Neovascularization

Mixed Follicles and Papillae; Upper tarsal scarring Palpebral Conjunctival Mixed Follicles and Papillae
17 IOP (@ 3:41pm) 18

Table 2. Recordings from the Ophthalmological Consults.

 

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Corneal hypersensitivity associated with blepharokeratoconjunctivitis in a post-partum female adult