Conjunctival Inclusion Cyst

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Conjuctival inclusion cysts are thin walled benign cystic lesions, lined with a non-keratinizing epithelium containing serous fluid and slowly progressing cysts. They are usually symptomless but can cause cosmetic disfigurement, reduced motility, foreign body sensation and dry eye due to unstable tear film when they increase in size.

Disease Entity

Conjunctival inclusion cyst developed after a trabeculectomy surgery, measuring approximately 1.5 mm. Note deposition of epithelial cells forming a pseudohypopyon.
Conjunctival Cyst
ICD-9 DATA 372.75
ICD-10 DATA H11.44

Conjunctival Cyst is recognized by the following codes as per the International Classification of Diseases (ICD) nomenclature:

ICD-9

ICD-10

  • ICD-10 DATA
    • H11.44 Conjunctival Cysts
    • H11.441 Conjunctival cysts, right eye
    • H11.442 Conjunctival cysts, left eye
    • H11.443 Conjunctival cysts, bilateral
    • H11.449 Conjunctival cysts, unspecified eye


Other links

Figure 1. Perilimbic conjunctival inclusion cyst, formed two years after a pterygium surgery with conjunctival grafting at the same site. Hospital of State Civil Servant (IAMSPE-SP).

Disease

Inclusion cysts are benign cysts filled with clear serous fluid containing shed cells or mucous material ( Figure 1).[1]Inclusion cysts constitute 80% of all cystic lesions of the conjunctiva. The average onset age is 47 and occurrence is equally in both sexes.[2]

They are formed from an inclusion of the conjunctival epithelium into the proper substance, forming a central cystic cavity due to epithelial cell proliferation. Cyst wall is composed of non-keratinized lining epithelium and connective tissue. [3]They can be either primary or secondary, and are usually asymptomatic. Treatment is required if discomfort develops or any impairment of function due to the size, but treatment is usually expectant.[1]

Etiology

Primary conjunctival inclusion cysts are congenital, and secondary cysts can be spontaneous or, most commonly, due to inflammatory conditions of the conjunctiva[4], such as pterygium, pingueculitis[5], chronic keratoconjunctivitis[6] and pyogenic granuloma[7], or following ocular trauma[8] or surgery, such as cataract [9], strabismus[10], enucleation[11] or scleral buckle placement[12].

Risk Factors

The following causes have been cited for secondary conjunctival inclusion cyst:

  • Inflammatory conditions of the conjunctiva (e.g. pterygium, pingueculitis[5], chronic keratoconjunctivitis[6] or pyogenic granuloma[7])
  • Trauma[8]
  • Surgery[9][10][11][12]
  • Sub-Tenon anesthesia[13]

General Pathology

Figure 2A. Image illustrating a patient who developed conjunctival nasal inclusion cyst after blunt trauma. Photo by courtesy of Maria Emília Xavier dos Santos Araújo PhD, Hospital of State Civil Servant, São Paulo (IAMSPE-SP).

According to Stedman's Medical Dictionary definition, cyst means an abnormal vesicle containing gas, fluid or semi-solid material, with a membranous framework. It can be developed in various locations e.g., eyelids, conjunctiva and anterior segment.[14] Post-traumatic or surgery cystic formation are often seen.[15]

Conjunctival inclusion cysts are derived from an inclusion of the conjunctival epithelium into the proper substance, forming a central cystic cavity due to epithelial cell proliferation. Cyst wall is composed of layers of non-keratinized lining epithelium and connective tissue.[3]

Pathophysiology

Excessive invagination of the caruncular epithelium or fornix during embryonic development leads to the formation of the primary inclusion cyst.[16] The presentation of these cysts varies from birth to old age.[4] On the other hand, secondary inclusion cysts can occur either naturally or under inflammatory condition of the conjunctiva. Anything that develops detachment of a portion of conjunctival epithelium, can cause a secondary inclusion cyst, such as surgery or trauma.[8] Sub-Tenon anesthesia has also been described as a possible cause.[13]

Figure 2B. Image illustrating a patient who developed conjunctival nasal inclusion cyst after blunt trauma. Photo by courtesy of Maria Emília Xavier dos Santos Araújo PhD, Hospital of State Civil Servant, São Paulo (IAMSPE-SP).

In addition, it is known that cystic formation depends on inflammatory processes, therefore the immune system is responsible for the outbreak of these processes. Individual factors, such as autoimmune diseases, can also contribute to change immune response resulting in tissue-damaging immune processes.[15]

Primary prevention

Primary conjunctival inclusion cysts cannot be prevented, as it is a congenital disease. Avoiding conjunctival inflammatory processes and ocular trauma can reduce the chance of developing a secondary inclusion cyst.

Diagnosis

History

Patient may be asymptomatic, being diagnosed with inclusion conjunctival cyst as an examination finding, or symptomatic. In symptomatic cases, patient may complain of a "round lesion" inside the eye, which may be associated with an increased cyst size or foreign body sensation. It is also common a previous history of ocular trauma or surgery.

Physical examination

Figure 4. Same patient from figure 1. Slit lamp photograph illustrating a pseudohypopyon in a conjunctival inclusion cyst, developed 2 years after pterygium excision with autologous conjunctiva transplantation. There is fluid of epithelial cells depositing in the bottom of the cyst and forming a pseudohypopyon. Hospital of State Civil Servant (IAMSPE-SP).


Diagnosis of conjunctival inclusion cyst is essentially clinical. Typical clinical features consist of painless cystic round lesion from small to moderate size.[4] The histopathological examination ratifies the diagnostic hypothesis. It is important to perform a complete eye examination: external exam (Figure 3A), visual acuity, extrinsic eye motility, pupillary reflexes, slit lamp examination (measuring the size of the cyst, assessing characteristics of its wall and internal content) (Figure 3B). It is also important to evaluate signs of previous trauma or previous eye surgery, or active inflammatory processes.

Figure 3. Large conjunctival inclusion cyst in the lower conjunctiva.

Figure 3A. Spontaneous cyst, developed without a previous history of trauma/surgery or chronic inflammation. Hospital of State Civil Servant (IAMSPE-SP).
Figure 3B. Slit lamp photograph. Note translucency of the conjunctival inclusion cyst wall. Hospital of State Civil Servant (IAMSPE-SP).

Signs

During examination, conjunctival inclusion cysts present as a cystic lesion that originates from the conjunctiva. It usually presents with a thin-translucent wall (Figure 3B). If the fluid contains epithelial cells, they can go to the bottom of the cyst and form a pseudohypopyon (Figure 4).

Symptoms

Small conjunctival inclusion cysts are generally asymptomatic or only cause mild sensations indicating the presence of a foreign body. Larger cysts can cause pain, motility disturbance, visual defect or refractive error, and cosmetics concerns.

In a clinical-histopathological study that analyzed different varieties of conjunctival cysts[4], the most common symptoms were, in decreasing order:

  1. Progressive increase in cyst size
  2. Cosmetic disfigurement
  3. Foreign body sensation
  4. Proptosis
  5. Ocular motility restriction
  6. Blurred vision

Clinical diagnosis

Diagnosis is based on previous history and physical examination.

Diagnostic procedures

The diagnosis of conjunctival inclusion cyst is clinical and confirmed by anatomopathology; however, there are some imaging diagnostics that can be useful. Corneal and conjunctival tumors can be visualized by AS-OCT and UBM, two noninvasive imaging techniques. [17]The use of imaging modalities is helpful for both preoperative planning and surgical decision-making and, also, to confirm cystic characteristics. Several studies on the quality of AS-OCT and UBM show that these imaging techniques provide useful information about the internal features, extension, size, and shape of cysts.

Ultrasound biomicroscopy (UBM)

UBM is a high-resolution noninvasive method, of great value for the diagnosis of anterior chamber cystic lesions, assessing their content (whether hypodense or hyperreflective) and can also be used to determine anatomical relations of the cyst with adjacent structures,[18] differentiating them from solid lesions, such as iris tumors or ciliary body tumors extending to the iris. [19] Through UBM examination, it is possible to define whether the cyst has primary or secondary origin. Consuelo et al., observed that secondary implantation cysts have relatively thick walls and that their content may be hypodense (translucent) with several particles in suspension (probably desquamating epithelial cells - Figure 4) or arranged in hyperreflective concentric layers corresponding to keratin lamellae. On the other hand, primary cystic lesions were characterized by presenting a thin, highly reflective wall, with hypodense content, besides having the character of being multiple and bilateral.[20]


Figure 5.  Conjunctival cyst after vitreoretinal surgery with silicone oil insertion.  Ultrasound biomicroscopy 50 MHZ transducer, immersion technique. 

Figure 5A. UBM longitudinal scan demonstrates an elevated round shaped cystic lesion at the limbal area, filled by hyporeflective content (*) and an inferior deposit of punctiform particles (thick arrow).  Note highly reflective deposit at the angle, endothelial line and iris surface (thin arrow). Photo courtesy of Norma Allemann PhD. Department of Ophthalmology, Federal University of São Paulo, Brazil.
Figure 5B. UBM cross-section of the cystic lesion, hyporreflective content (*) and an inferior deposit with punctiform particles (thick arrow).  The posterior limit with the sclera is easily detected. Photo courtesy of Norma Allemann PhD. Department of Ophthalmology, Federal University of São Paulo, Brazil.


Anterior Segment Optical Coherence Tomography (AS-OCT)

AS-OCT is ideal for imaging structures from the surface of the eye to the level of the iris. [21]A disadvantage of AS-OCT is that it cannot visualize structures behind pigmented lesions, like the iris, and cannot visualize early pathological changes smaller than 5 μm such as early dysplasia.[21][22]When comparing AS-OCT and UBM, AS-OCT is the better imaging technique for small cystic structures. This is especially useful for nevi as they often contain small cysts. In contrast, UBM is a better technique to determine the tumor margins.


Figure 6.   Asymptomatic bulbar conjunctival inclusion cyst at the nasal area. 

Figure 6A. Biomicroscopy of a round well-delimited subconjunctival lesion. Photo by courtesy of Norma Allemann PhD. Department of Ophthalmology, Federal University of São Paulo, Brazil.
Figure 6C.  Cross-section of the lesion and posterior light attenuation artifacts. AS-OCT Visante, Zeiss.Photo by courtesy of Norma Allemann PhD. Department of Ophthalmology, Federal University of São Paulo, Brazil.
Figure 6B. Longitudinal AS-OCT section demonstrating a round lesion with hyporreflective content (punctiform particles noticed) and a thin hyperreflective wall.  Note posterior light attenuation artifacts.AS-OCT Visante, Zeiss. Photo by courtesy of Norma Allemann PhD. Department of Ophthalmology, Federal University of São Paulo, Brazil.


Comparison of UBM and AS-OCT showed that UBM had a better tumor visualization and better resolution of the posterior margin. UBM also had a better resolution for pigmented as well as for nonpigmented tumors. However, AS-OCT showed better resolution of the anterior border and better resolution of the anterior segment anatomy. Posterior tumor shadowing was rarely found in UBM images and more common in AS-OCT. The image quality was good in UBM but less in AS-OCT. This study shows that AS-OCT is superior to UBM for the imaging of conjunctival lesions, because AS-OCT offers a higher resolution and conjunctival lesions are superficial and mostly not pigmented.[17][23]

Laboratory test

Conjunctival Inclusion Cysts are diagnosed clinically, therefore, laboratory tests are not required.

Histopathology

Figure 7. Histological sections of conjunctival inclusion cyst resection. Same patient from Figure 3.

Figure 7A. Panoramic photo view. Photo by courtesy of Ulisses de Alcantara Ferreira, M.D. Pathology Sector, Hospital of State Civil Servant (IAMSPE-SP).
Figure 7B. Two-layer-lined conjunctival non-keratinized epithelium, with goblet cells. HE - 40x. Photo by courtesy of Ulisses de Alcantara Ferreira, M.D. Pathology Sector, Hospital of State Civil Servant (IAMSPE-SP).
Figure 7D. Two-layer-lined conjunctival non-keratinized epithelium, with goblet cells. HE - 100x. Photo by courtesy of Ulisses de Alcantara Ferreira, M.D. Pathology Sector, Hospital of State Civil Servant (IAMSPE-SP).
Figure 7C. Cyst lined by stratified epithelium with goblet cells (arrows) on the cyst wall, communicating directly with the lumen. HE - 100x. Photo by courtesy of Ulisses de Alcantara Ferreira, M.D. Pathology Sector, Hospital of State Civil Servant (IAMSPE-SP).


The American Academy of Ophthalmology's Pathology Atlas contains a virtual microscopy image of Conjuctival Inclusion Cyst .

Differential diagnosis

Benign
  • Conjunctival papilloma
  • Papilloma of caruncle
  • Conjunctival pseudoepitheliomatous hyperplasia
  • Keratoacanthoma
  • Conjunctival hereditary benign intraepithelial dyskeratosis
  • Conjunctival dacryoadenoma
  • Epithelial inclusion cyst
Premalignant
  • Conjunctival keratotic plaque
  • Actinic keratosis
  • Conjunctival intraepithelial neoplasia

Check Eyewiki´s Conjunctival Epithelium Neoplasms page for differential diagnosis.

Management

Conduct can either be expectant or interventionist, depending on the size of the cyst and the patient's complaint.

General treatment

Excision of conjunctival inclusion cyst is the definitive treatment. In cases where patient presents to emergency room with a complaint of eye discomfort, it is possible to aspirate the cyst in the slit lamp, under topical anesthesia of the ocular surface with 0.5% proparacaine, using a 27 gauge needle for this purpose. Care must be taken not to puncture the eyeball during the procedure. Patient should be referred for surgical treatment and follow up even after the procedure.

Medical therapy

Figure 8. 8A. Clinical photography of an anophthalmic patient. Poor positioning of prosthesis and copious discharge before treatment. 8B. Socket of the same patient before treatment showing multiple conjunctival cysts. 8C. Improved positioning of the prosthesis and discharge after treatment. 8D. Socket of the same patient after treatment showing disappearance of cysts. Reproduced from Bagheri A, Shahraki K, Yazdani S. Trichloroacetic acid 10% injection for treatment of conjunctival inclusion cysts. Orbit. 2020; 39(2):107-111.
Figure 9. Paired injection technique: syringe 1 is use to withdraw the cyst content; syringe 2 is use to inject the alcohol. Reproduced from Kothari M. A novel method for management of conjunctival inclusion cysts following strabismus surgery using isopropyl alcohol with paired injection technique. J AAPOS. 2009 Oct;13(5):521-2.[24]

Generally, these cysts may disappear spontaneously; however, persistent cases require treatment. Surgical excision of the cyst is the best treatment, but thermal cautery under slit-lamp visualization[25] or YAG laser of the cyst can also be performed.[9][26]

There are reports on the application of TCA (trichloroacetic acid ) 20–25% for superficial conjunctival cysts with high success rates, and also reports of TCA 10% injection  into conjunctival cysts in ophthalmic and anophthalmic sockets, including children and multiple cysts, with 100% success (Figure 8).[27] Also, Mihir Kothari et al. reported two cases of conjunctival inclusion cysts following strabismus surgery treated using paired injection technique, which consists of using two 31 G insulin syringes, one empty syringe (syringe 1) and the other filled with 0.5 mL 70% isopropyl alcohol (syringe 2), simultaneously. The fluid from the cyst is aspirated into syringe 1 as the cyst is simultaneously filled with the alcohol from syringe 2 to prevent collapse. Once all the alcohol from syringe 2 is injected, aspiration (syringe 1) is stopped. The cyst remains inflated and filled with alcohol throughout the procedure. Thirty seconds later, the cyst is emptied by aspirating the alcohol with syringe 1 (Figure 9). There was no recurrence in a nine-month-follow-up.[24]

Nejat et al., treated five eyes with conjunctival cysts using atmospheric low-temperature plasma (ALTP) - PANIS method (plasma-assisted non-invasive surgery). Procedure was started by applying a plasma spot on the highest point of the cyst, and then other spots applied in a spiral at the base of the cyst to debulk it. The conjunctival cysts were removed using the white handpiece of the plasma generator device (Plexr, GMV s.r.l Grottaferrata, Italy). They concluded that ALTP can be used as a new approach to treating conjunctival cysts.[28]

Supplementary video of a case series paper "A Novel Approach to Treatment of Conjunctival Cyst Ablation using Atmospheric Low-Temperature Plasma" published in the open access journal Clinical Ophthalmology by Farhad Nejat, Khosrow Jadidi, Shiva Pirhadi et al.[28]

Surgery

Excision of the conjunctival inclusion cyst can be performed under topical local anesthesia with 0.5% proparacaine, associated with subconjunctival infiltration of lidocaine around the cyst. A non-traumatic tweezer can be used to assist in the divulsion step. A small incision is made and the blunt tip of scissors introduced between the cyst and Tenon capsule, to separate the cyst from the surrounding tissue. After total divulsion in all circumference, next step is to carefully divulse the base of the cyst, as ruptures are common during dissection. Depending on the size of the cyst, the excess tissue is removed. Removing the cyst intact decreases chances of recurrence. There are some options in relation to the exposed scleral bed: it is possible to use the bare sclera technique, which consists of allowing the bare scleral bed to re-epithelialize, using autologous conjunctival transplant or amniotic membrane. Lastly, refer the material to anatomopathological examination.

Check the videos below for a better understanding:

1) Surgery video from Figure's 1 patient.

2) This video illustrates the removal of a conjunctival inclusion cyst in inferior fornix, similar to the patient's cyst in Figure 2.

Reproduced from Dr. Neeraj Sharma, Aravind Eye Hospital


3) This video demonstrates the simple technique of conjunctival epithelial cyst removal without sutures.

Reproduced from Dr. Manju Meena, Pink City Eye and Retina Centre, Jaipur, India.

Figure 12. Same patient as above. Hospital of State Civil Servant (IAMSPE-SP).

Surgical follow up

The follow-up time for each patient who underwent surgical excision of the cysts varies. It is recommended a minimum period of 1 year after surgery to assess the recurrence and development of any complications. The figure below (Figures 11 and 12) illustrates patient 2 months after excision.

Complications

As the cysts are thin walled, rupture is common during excision. Recurrence is the main postoperative concern. Careful and intact removal of cyst is necessary to prevent recurrence.[4]

Prognosis

Prognosis for conjunctival inclusion cyst is commonly good.

Additional Resources

  • Images ilustrating conjunctival inclusion cyst (A) and histopathological (B).
    © 2021 American Academy of Ophthalmology

A: Epithelial inclusion cysts may follow conjunctival trauma.

B: The cyst is lined by nonkeratinizing, stratified squamous epithelium, consistent with conjunctiva.

You can also visit AAO website to check out this multimedia.

  • Here is a video showing a large, translucent cyst on the conjunctiva of the eye. This is most likely an epithelial inclusion cyst. These occur when epithelial cells are trapped under the conjunctiva (from prior surgery) and continue to produce mucinoid secretion. This was removed via excision with an attempt to remove the entire cyst wall to prevent recurrence. Reproduced from Tim Root Virtual Eye Professor. https://timroot.com/conjunctival-inclusion-cyst-video/




References

  1. 1.0 1.1 Nath K, Gogi R, Zaidi N, Johri A. Cystic lesions of conjunctiva (a clinicopathogical study). Indian J Ophthalmol. 1983: 31(1):1-4.
  2. 2. Lu J, Chu F, Chen K. Conjunctival Inclusion Cyst. Hong Kong Journal of Emergency Medicine. 2013;20(3):184-185.
  3. 3.0 3.1 Johnson DW, Bartley GB, Garrity JA, Robertson DM. Massive epithelium-lined inclusion cysts after scleral buckle. Am J Ophthalmol. 1992;113(4): 439-42.
  4. 4.0 4.1 4.2 4.3 4.4 Thatte S, Jain J, Kinger M, Palod S, Wadhva J, Vishnoi A. Clinical study of histologically proven conjunctival cysts. Saudi J Ophthalmol. 2015;29(2):109-115.
  5. 5.0 5.1 Dias VG, Martins MP, Bezzon AKT, Aguni JS, Cavalheiro R. Cisto de inclusão conjuntival gigante associado a pterígio: relato de caso. Arq. Bras. Oftalmol. 2004;67(5):831-833.
  6. 6.0 6.1 Lee Seung-Won, Lee Seung-Chan, Jin Kyung-Hyun. Conjunctival inclusion cysts in long standing chronic vernal keratoconjunctivitis. Korean J Ophthalmol. 2007;21(4)
  7. 7.0 7.1 Suzuki K, Okisaka S, Nakagami T. The contribution of inflammatory cell infiltration to conjunctival inclusion cyst formation. Nippon Ganka Gakkai Zasshi. 2000;104(3):170-3.
  8. 8.0 8.1 8.2 Barishak Robert Y., Barrak E., Lazar M. Episcleral traumatic conjunctival inclusion cyst. BJO. 1977;61:29–301
  9. 9.0 9.1 9.2 Narayanappa S, Dayananda S, Dakshayini M, Gangasagara SB, Prabhakaran VC. Conjunctival inclusion cysts following small incision cataract surgery. Indian Journal of Ophthalmology. 2010;58(5):423-425.
  10. 10.0 10.1 Metz HS, Searl S, Rosenberg P, Sterns G. Giant orbital Cyst after strabismus surgery. J AAPOS. 1999;3(3):185-7.
  11. 11.0 11.1 Jünemann A, Holbach LM. Epitheliale Riesenimplantationszyste 50 jahre nach Enukleation ohne Orbitaimplantat. Kin Monatsbl Augenheilkd. 1998;212 (2):127-8.
  12. 12.0 12.1 Johnson DW, Bartley GB, Garrity JA, Robertson DM. Massive epithelium-lined inclusion cysts after scleral buckle. Am J Ophthalmol. 1992;113(4): 439-42.
  13. 13.0 13.1 Vishwanath M.R., Jain A. Inclusion cyst after subtenon. Br J Anaesthesia. 2005;95:825–826.
  14. Stedman TL. Cyst. In: Stedman TL. Stedman's medical dictionary. 26th ed. Baltimore: Williams & Wilkins; 1995. p.429.  
  15. 15.0 15.1 Dias VG, Martins MP, Bezzon AKT, Aguni JS, Cavalheiro R. Cisto de inclusão conjuntival gigante associado a pterígio: relato de caso. Arquivos Brasileiros de Oftalmologia 2004; 67(5): 831-833.
  16. Imaizumi M, Nagata M, Matsumoto CS, Nakalruka K, Kachima K. Primary conjunctival epithelial cyst of orbit. Int Ophthalmol. 2007;27:269–271.
  17. 17.0 17.1 Janssens K, Mertens M, Lauwers N, de Keizer RJ, Mathysen DG, De Groot V. To Study and Determine the Role of Anterior Segment Optical Coherence Tomography and Ultrasound Biomicroscopy in Corneal and Conjunctival Tumors. J Ophthalmol. 2016;2016:1048760.
  18. Allemann N. Biomicroscopia ultra-sônica. Arq Bras Oftalmol. 1995;58:283-5
  19. Pavlin CJ. Practical application of ultrasound biomicroscopy. Can J Ophthalmol 1995;30:225-9.
  20. Consuelo ABD, Chojniak MMM, Allemann N. Ultrasound biomicroscopy and secondary epithelial downgrowth cysts of anterior chamber. Arq. Bras. Oftalmol.1998;61( 6 ): 656-661.
  21. 21.0 21.1 Garcia JPS, Rosen RB. Anterior segment imaging: optical coherence tomography versus ultrasound biomicroscopy. Ophthalmic Surgery Lasers and Imaging. 2008;39(6):476–484.
  22. Salim S. The role of anterior segment optical coherence tomography in glaucoma. Journal of Ophthalmology. 2012;2012:9.
  23. Bianciotto C, Shields CL, Guzman JM, et al. Assessment of anterior segment tumors with ultrasound biomicroscopy versus anterior segment optical coherence tomography in 200 cases. Ophthalmology. 2011;118(7):1297–1302.
  24. 24.0 24.1 Kothari M. A novel method for management of conjunctival inclusion cysts following strabismus surgery using isopropyl alcohol with paired injection technique. J AAPOS. 2009 Oct;13(5):521-2.
  25. Hawkins AS, Hamming NA. Thermal cautery as a treatment for conjunctival inclusion cyst after strabismus surgery. J AAPOS. 2001 Feb;5(1):48-9.
  26. de Bustros S, Michels RG. Treatment of acquired epithelial inclusion cyst of the conjunctiva using the YAG laser. Am J Ophthalmol. 1984 Dec 15;98(6):807-8.
  27. Bagheri A, Shahraki K, Yazdani S. Trichloroacetic acid 10% injection for treatment of conjunctival inclusion cysts. Orbit. 2020 Apr;39(2):107-111.
  28. 28.0 28.1 Nejat F, Jadidi K, Pirhadi S, Adnani SY, Nabavi NS, Nejat MA. A Novel Approach to Treatment of Conjunctival Cyst Ablation Using Atmospheric Low-Temperature Plasma. Clin Ophthalmol. 2020;(14):2525-2532.