[Evaluation of the accuracy of clinical diagnosis of conjunctival neoplasms : Comparison with histological findings after excision]. / Untersuchung der Genauigkeit klinischer Diagnosen von Neoplasien der Konjunktiva : Vergleich mit den histologischen Befunden nach Exzision.

BACKGROUND: Neoplasms of the conjunctiva include many different entities with a broad variety of clinical presentations. This can make a precise clinical diagnosis difficult. R0 resection is the gold standard treatment for most malignant conjunctival neoplasms, but not every benign lesions must treated by excision. In clinical practice it is important to make an accurate clinical diagnosis to enable the best possible management of conjunctival neoplasms. OBJECTIVE: The aim of this study was to determine the accuracy of clinical diagnosis of neoplasms of the conjunctiva. MATERIALS AND METHODS: Within a retrospective design, the data from all patients with excision of a conjunctival lesion between 2011 and 2020 in the Department of Ophthalmology of the UKSH Campus Kiel were extracted and analyzed. The specificity, sensitivity, and positive and negative predictive value for the preoperative clinical rating of dignity and diagnosis were evaluated based on the histological diagnostic findings. RESULTS: Of 220 included cases, 75% were benign and 25% malignant. The most frequent neoplasm of the conjunctiva was benign conjunctival nevus. The sensitivity for clinical prediction of a benign lesion was 0.86 (95% confidence interval [CI] 0.59-0.92), the specificity 0.95 (CI 0.85-0.99), and the positive predictive value 0.98 (CI 0.94-1.0). The sensitivity for clinical prediction of malign dignity was 0.95 (CI 0.85-0.99), the specificity 0.88 (CI 0.83-0.93), and the positive predictive value 0.73 (CI 0.61-0.83). CONCLUSION: The derived values for clinical diagnosis of conjunctival neoplasms can be rated as good. However, in clinical practice, untypical lesions can be hard to diagnose correctly, and the clinical diagnosis should be carefully reviewed; if in doubt, excision should be preferred.

Conjunctival myxoma: A case report and review of a rare tumor.

RATIONALE: Conjunctival myxoma is a rare benign tumor, which can mimic more common conjunctival lesions such as a cyst, lymphangioma, amelanotic nevus, neurofibroma, amelanotic melanoma, or lipoma. We describe a patient with the conjunctival myxoma, who was initially misdiagnosed as a conjunctival cyst. This case report includes intraoperative photographs and various immunohistochemical staining images. PATIENTS CONCERNS: A 55-year-old woman presented with a painless mass in the superotemporal conjunctiva of the left eye, which she had noticed 1 month ago. The patient had no previous history of trauma or eye surgery. Slit-lamp examination revealed a well-circumscribed, freely movable, pinkish, semi-translucent mass on the temporal bulbar conjunctiva, suggestive of a conjunctival cyst. DIAGNOSES: Histopathological analysis showed stellate- and spindle-shaped cells within the loose myxoid stroma, confirming a diagnosis of conjunctival myxoma. INTERVENTIONS: The conjunctival lesion was completely excised under local anesthesia. OUTCOMES: After 4 months of follow-up, the patient remained in good health without recurrence of the conjunctival lesion and no evidence of any systemic abnormality. LESSONS: Myxoma is an extremely uncommon benign tumor derived from primitive mesenchyme. Considering the rarity of the tumor and its similarity to other conjunctival tumors, diagnosis can be challenging. Ophthalmologists should consider myxoma as a possible differential diagnosis when encountering conjunctival lesions. Surgical excision is essential to confirm the diagnosis and careful systemic evaluation is required to prevent potentially life-threatening underlying systemic conditions.

Conjunctival melanoma: Insights into classification, outcomes, and biomarkers.

Conjunctival melanoma is quite rare, estimated at approximately 0.5 incidence per 1 million persons per year. This malignancy arises from a pre-existing nevus (7%), primary acquired melanosis (74%), or de novo without pre-existing condition (19%) and develops most often in patients with Fitzpatrick skin types I (23%) and II (62%). At initial presentation, the tumor size is approximately 13 mm in cross-sectional diameter and has 3-mm thickness, involving the bulbar (97%), forniceal (30%), tarsal (28%), or caruncular (11%) regions, often with corneal (54%) and rarely with orbital (4%) involvement. According to the eighth edition of the American Joint Committee on Cancer (AJCC), the tumor is classified as T1 (63%), T2 (18%), T3 (20%), and T4 (0%). Outcomes depend on several factors including patient age, AJCC classification, orbital invasion, and type of initial surgery, whereas tumor origin and Fitzpatrick skin type do not appear to impact outcomes. Older patients (≥70 years of age) demonstrate larger tumors, greater recurrence, and greater vision loss. Analysis of 425 patients by AJCC classification (T1 versus T2 versus T3) revealed increasing T category with greater lymph node metastasis (3% versus 13% versus 25%; P < .001), tumor-related systemic metastasis (13% versus 45% versus 40%; P < .001), and tumor-related death (8% versus 22% versus 37%; P < .001). Data of patients with orbital invasion revealed significantly greater 10-year rates of exenteration (P < .001), distant metastasis (P = .0005), and death (P = .001). Studies have demonstrated biomarkers related to conjunctival melanoma include mutations in BRAF, NRAS, ATRX, and NF1. Future therapies might be directed against these mutations or with small-molecule inhibitors and/or immunotherapy. In summary, conjunctival melanoma is a rare but ominous malignancy, imparting moderate risk for lymph node and systemic metastasis as well as death, depending on tumor features and classification. The first surgery is highly important in prevention of tumor seeding, recurrence, and metastasis.

Histopathological Results of Conjunctival Masses with Suspected Malignancy Based on Slit-lamp Biomicroscopy.

OBJECTIVE: To evaluate the histopathological results of conjunctival masses suspected to be malignant based on biomicroscopic examination. STUDY DESIGN: Observational study. Place and Duration of the Study: Department of Ophthalmology, Celal Bayar University, Hafsa Sultan Hospital, Manisa, Turkiye, from November 2013 to February 2021. METHODOLOGY: Patients who underwent excision for the diagnosis and treatment of conjunctival surface masses with clinical suspicion of malignancy were evaluated retrospectively. The masses were categorised as benign, premalignant, and malignant lesions according to the histopathological results. The distribution of conjunctival masses was analysed according to patients' gender and age groups. RESULTS: The study included 98 conjunctival masses in 98 patients (57.1% men, mean age 48.6±21.85 years). On pathological examination, 63 of the masses were found to be benign (64.3%), 22 were premalignant (22.4%), and 13 were malignant (13.3%). The most common benign lesion was nevus (n=21, 21.4%). All detected premalignant lesions were conjunctival intraepithelial neoplasms (CIN), detected in 22 patients (22.4%). Of these, 13 patients (13.3%) had carcinoma in situ (CIN III). Thirteen (13.3%) of the masses were malignant, the most common being squamous cell carcinoma (n=10, 10.2%). The frequency of premalignant and malignant lesions increased with age (p<0.001). There was no statistical relationship between malignancy and gender (p=0.619). CONCLUSION: Most conjunctival masses in this series were benign, with nevi being the most common. The most common premalignant and malignant lesions were intraepithelial neoplasia and squamous cell carcinoma, respectively. Malignant conjunctival lesions were more common in older patients. KEY WORDS: Conjunctival nevus, Conjunctival intraepithelial neoplasia, Squamous cell carcinoma.

Pigmented lesions of the conjunctiva: The sheep and the wolf.

Background: Pigmented lesions in the conjunctiva can be baffling to both the patients and the treating ophthalmologist because of their varied range of presentation and overlapping clinical features. The lesions range from incidental pigment deposition such as mascara and complexion-associated melanosis to malignant melanoma which poses a risk to life. Similarly, the management ranges from observation at regular intervals to aggressive surgery like exenteration. Purpose: We wanted to present a crisp and precise video of the good, bad, and ugly pigmented lesions of the conjunctiva, highlighting their specific clinical features important for the diagnosis and their management. Synopsis: This video describes the myriad of pigmented conjunctival lesions, their diagnostic characteristics, and management based on oncological principles. Link: https://drive.google.com/file/d/1BYJ51rQtqjwM6e73BwrrLqdC1EoXA8Eu/view?usp=sharing. Highlights: : Pigmented lesions can have variable presentation and close mimics, therefore, it is important to differentiate and identify the lesions accurately. This video highlights different pigmented lesions and their individual characteristic features. Video link https://youtu.be/m9tt7dx9SWc.

Clinical features and factors affecting prognosis and partial deterioration of ocular papilloma: a retrospective study of 298 cases.

PURPOSE: This study aimed to analyze the clinicopathological features of ocular papilloma, a common benign tumor, and the risk factors related to its recurrence and partial deterioration. METHODS: We collected and analyzed the clinical information of 298 patients (51.68% males) with mean age of 41.54 ± 21.95 years, in the ophthalmology department of the West China Hospital. Clinical and pathological factors that might be related to papilloma recurrence and partial deterioration were studied. RESULTS: The top three papilloma sites were bulbar conjunctiva, eyelid skin and palpebral conjunctiva. Moreover, 3.59% of lesions presented a malignant transformation, and 16.28% of patients had one or more recurrences after an average follow-up of 4.47 years. The multivariate logistic regression model showed that multiple lesions were a risk factor for recurrence (p = 0.022, OR = 3.088, 95% CI: 1.180-8.079), while cryotherapy decreased the recurrence risk (p = 0.044, OR = 0.364, 95% CI: 0.136-0.972). Additionally, elderly patients and lesions on the corneal limbus or cornea had a higher risk of malignant transformation (p = 0.004 and 0.01, OR = 1.086 and 7.827, 95% CI: 1.027-1.150 and 1.629-37.596, respectively). CONCLUSION: Ocular papilloma usually occurs in middle-aged and young patients, with no significant gender differences. Older patients and lesions on the corneal limbus or cornea are risk factors for partial malignant transformation. Finally, multiple lesions were a risk factor for recurrence, and cryotherapy reduced the recurrence rate.

Mucocutaneous subdermal plexus flap for complete excision of a malignant dermal and conjunctival melanoma in a dog.

PURPOSE: To perform a reconstructive blepharoplasty to obtain complete surgical excision of a darkly pigmented raised conjunctival-eyelid mass of the lower eyelid in a dog. ANIMAL STUDIED: A 7-year-old, female-spayed, Yorkshire Terrier was evaluated for a slowly progressive, dark brown-to-black raised mass of the lower left eyelid. Sampling of the mass via fine-needle aspirate or incisional biopsy was declined, and an excision of the mass with the goal to obtain complete margins and maintain normal eyelid function with cosmesis was elected. PROCEDURES: The lower palpebral conjunctival-eyelid pigmented mass was excised en bloc and the lower eyelid was reconstructed with a mucocutaneous subdermal plexus flap. RESULTS: Histopathology revealed a malignant dermal and conjunctivalmelanoma excised with complete margins (1-2 mm). Short-term complications included corneal ulceration and eschar formation, which resolved completely at the 1-month follow-up. Long-term complications included mild trichiasis with epiphora and porphyrin staining. Tumor recurrence was not observed during an 8-month follow-up period. CONCLUSIONS: The en bloc excision with mucocutaneous subdermal plexus flap was successful in obtaining complete surgical margins for a malignant conjunctival-eyelid melanoma. An excellent functional and cosmetic outcome was achieved without tumor recurrence during an 8-month follow-up period. A mucocutaneous subdermal plexus flap can be considered as a surgical option for malignant melanoma of the lower eyelid.

Conjunctival Autografts for Ocular Surface Reconstruction after Conjunctival Nevus Excision.

PURPOSE: The aim of this study was to evaluate the clinical and therapeutic outcomes of the cases where we used conjunctival autografts with and without the Tenon fascia for ocular surface reconstruction after conjunctival nevus excision. METHODS: This study included 63 eyes of 63 patients who underwent conjunctival nevus excision between January 2013 and December 2020. Although a Tenon-free conjunctival autograft was used in 32 eyes of 32 patients in group 1, a Tenon-containing conjunctival autograft was used in 31 eyes of 31 patients in group 2. The clinical and histopathological characteristics of the nevus, complete graft epithelization, cosmetic outcomes, and postoperative complications were evaluated. RESULTS: Conjunctival autografts were harvested from the contralateral eye in 3 eyes (9.3%) in group 1 and 2 eyes (6.4%) in group 2 ( P = 0.66). Postoperatively, the mean defect size at the harvest site was 5.3 ± 1.4 mm in group 1 and 5.5 ± 1.5 mm in group 2 ( P = 0.47). Graft edema was observed in only 1 case (3.1%) in group 1 and 6 cases (19.3%) in group 2 ( P = 0.04). Although a complete graft epithelization was observed in all eyes in group 1, fluorescein staining was present in 2 eyes (6.4%) in group 2 ( P = 0.14). Cosmetically, retracting and shrinking grafts were absent in group 1, whereas group 2 had in 4 eyes (12.9%) ( P = 0.03). Neither group had conjunctival scarring, symblepharon, eyelid cicatrization, dysmotility, or pannus at the donor site. CONCLUSIONS: Ocular surface reconstruction with a Tenon-free conjunctival autograft after conjunctival nevus excision provides excellent cosmetic and functional results without significant complications.

Sublimation of Benign Conjunctival Nevi Using Plasma-Assisted Noninvasive Surgery: A Clinical Case Series.

Background: Conjunctival nevi (CN) are common benign ocular tumors. Given their low risk of malignancy, surgical removal of nevi is primarily requested by patients. Herein, we introduce Atmospheric Low-temperature Plasma (ALTP) as a novel noninvasive method for the removal of CN. Methods: A clinical case series was conducted from 2020 to 2021 at the Vision Health Ophthalmic Center in Tehran, Iran. CN in one of the eyes of seven patients was treated. In all patients, the benignity of CN was confirmed by ocular oncologists. The white handpiece of the Plexr device, which generates plasma with the lowest output, was used to apply plasma spots on the nevi. In addition, the Ocular Surface Disease Index (OSDI) questionnaire was completed by all patients before and six months after the treatment. Results: In all patients, the nevi outside the limbus area completely disappeared. The mean size of pre- and post-operative nevi was 3.89×11.7 and 0.54×1.69 mm, respectively. Results of the OSDI questionnaire showed significantly lower scores after the surgery in all patients. Conclusion: The ALTP method is a simple, cost-effective, and office-based surgery to remove CN safely and effectively.

Analysis of ocular surface and quality of life in patients with corneal and conjunctival tumors.

PURPOSE: To evaluate the impact of corneal and conjunctival tumors on the ocular surface and quality of life of patients before and after surgical treatment. METHODS: This prospective study conducted a preoperative and 30- and 90-day postoperative assessment of patients diagnosed with conjunctival and corneal tumors. Demographic data were collected preoperatively. The 12-Item Short-Form Health Survey (SF-12) and Ocular Surface Disease Index (OSDI) questionnaires were applied to assess patients' quality of life and perception of their vision-related functions. The tear breakup time and Schirmer tests were performed for ocular surface evaluation. The tumor extensions were measured using ImageJ image analysis software. RESULTS: Twenty-three patients were enrolled. The mean age at examination was 52.8 ± 17.3 years (range: 27-9 years). The most common tumor type was squamous cell carcinoma (61.5%). The patients' visual acuity improved significantly at 1 month and 3 months (p=0.018 and p=0.036, respectively). No significant differences were found between tear breakup time and Schirmer tests preoperatively and at 3 months postoperatively (p=0.150 and p=0.490, respectively). The SF-12 scores demonstrated significant differences between the preoperative and 30- and 90-day postoperative mental components (p=0.008 and p=0.026, respectively). Tumor extension was 868.7 ± 344.9 pixels (range, 224.6-1481.6 pixels) and were significantly correlated with the preoperative (p=0.011), 30-day postoperative (p=0.017), and 90-day postoperative (p=0.012) SF-12 mental components, as well as the emotional component at the 30th postoperative day (p=0.016). CONCLUSION: Patients with corneal and conjunctival tumors improved their ocular symptoms, visual acuity, and the emotional component of their quality of life after surgical excision of the tumor.

Bilateral synchronous conjunctival myxoma and review of the literature.

PURPOSE: The purpose of this study was to report the clinicopathological features and management of the first case of bilateral synchronous conjunctival myxoma. METHODS: This study was a case report and literature review. RESULTS: A 66-year-old Chinese male with past ocular history of uncomplicated bilateral phacoemulsification and intraocular lens (IOLs) 3 years ago prior to presentation presented with bilateral red and swollen conjunctiva for over a year. On examination his corrected distance visual acuity (CDVA) was 25/20 in the right eye 20/20 in the left eye. Slit lamp examination revealed swollen temporal conjunctiva bilaterally which appeared as painless, well-circumscribed, salmon-pink, fleshy patches. The lesion in the right eye was subsequently excised, followed by excision of the lesion in the left eye at 3-week interval. Microscopically, histopathological examination of both excised specimens revealed hypocellular conjunctival mucosa covered by non-dysplastic epithelium, with presence of myxoid degeneration in the subepithelial stroma and immunostaining findings consistent with conjunctival myxoma. At his latest follow-up at 24 months, there were no recurrences of the conjunctival masses and the CDVA was the same as preoperatively.

Midterm results of conjunctival reconstruction with buccal mucosa and amniotic membrane after resecting ocular surface squamous neoplasia of the fornix.

OBJECTIVE: To evaluate the midterm results of tumour resection with or without adjunctive therapy for ocular surface squamous neoplasia of the fornix, including conjunctival reconstruction with buccal mucosa and amniotic membrane. METHODS: A retrospective case-series analysis including slit-lamp examination, photographic documentation, and biopsy results (repeated when clinical findings changed). Analysis centred on eye function, complications, additional procedures, and recurrence rate. Surgical technique included tumour resection and subsequent reconstruction of lost conjunctiva with buccal mucosa and amniotic membrane. RESULTS: We included 83 affected eyes from 76 patients (mean age, 63.10 ± 14.45 years; 34 females) seen over a mean follow-up period of 26.56 ± 21.17 months. We achieved bulbus oculi salvage in 82 eyes (98.79%) and typically preserved visual acuity (mean 0.2 ± 0.5 logMAR and 0.3 ± 0.5 logMAR at presentation and last follow-up, respectively). Moreover, only 23 patients (27.71%) required corrective surgery for clinically relevant complications. The main complications included symblepharon (9.64%; n = 8), cicatricial ectropion (9.64%; n = 8), pannus (9.64%; n = 8), and corneal decompensation (8.43%; n = 7). Local tumour recurrence was seen in 23 patients (27.71%). CONCLUSIONS: These midterm results confirm the efficacy of conjunctival reconstruction with amniotic membrane and buccal mucosa after resection of ocular surface squamous neoplasia from the fornix with palpebral and bulbar conjunctiva involvement. We not only achieved good tumour control and organ salvage with high levels of organ preservation but we also achieved good functional outcomes and acceptable recurrence rates. All clinically significant complications could be corrected in separate procedures.

Novel ocular immunotherapy induces tumor regression in an equine model of ocular surface squamous neoplasia.

Ocular surface squamous neoplasia (OSSN) is the major cause of corneal cancer in man and horses worldwide, and the prevalence of OSSN is increasing due to greater UVB exposure globally. Currently, there are no approved treatments for OSSN in either species, and most patients are managed with surgical excision or off-label treatment with locally injected interferon alpha, or topically applied cytotoxic drugs such as mitomycin C. A more broadly effective and readily applied immunotherapy could exert a significant impact on management of OSSN worldwide. We therefore evaluated the effectiveness of a liposomal TLR complex (LTC) immunotherapy, which previously demonstrated strong antiviral activity in multiple animal models following mucosal application, for ocular antitumor activity in a horse spontaneous OSSN model. In vitro studies demonstrated strong activation of interferon responses in horse leukocytes by LTC and suppression of OSSN cell growth and migration. In a trial of 8 horses (9 eyes), treatment with topical or perilesional LTC resulted in an overall tumor response rate of 67%, including durable regression of large OSSN tumors. Repeated treatment with LTC ocular immunotherapy was also very well tolerated clinically. We conclude therefore that ocular immunotherapy with LTC warrants further investigation as a novel approach to management of OSSN in humans.

Ocular surface squamous neoplasia in a patient following oral steroids for contralateral necrotising scleritis.

A male patient in his 70s presented with left eye necrotising scleritis. His ocular history was significant for pterygium excision with mitomycin C 3 months prior in the affected eye, open-angle glaucoma, nuclear sclerosis cataract and previous sixth cranial nerve palsy. Scleral culture was negative and blood work was positive for rheumatoid factor and HLA-B27. The patient was treated for necrotising scleritis with oral doxycycline, vitamin C, ranitidine and prednisone with gradual taper over 45 days. Two months after initiating treatment, his necrotising scleritis achieved complete resolution; however, a new-onset ocular surface squamous neoplasia (OSSN) was identified at the temporal limbus of the contralateral eye. He was treated with topical interferon alpha-2b 1 million IU qid and achieved complete resolution after 4 months. The case highlights both the acute precipitation of OSSN following oral steroids and a sight-threatening complication following pterygium excision.

Topical pharmacotherapy for ocular surface squamous neoplasia: systematic review and meta-analysis.

Ocular surface squamous neoplasia (OSSN) has different treatment modalities. Although surgical excision has been the gold standard therapeutic option, topical pharmacotherapy agents such as 5-fluorouracil (5-FU), interferon alfa-2b (IFN) and mitomycin-C (MMC) are also commonly used. The protocol was registered (CRD42021224961). Comprehensive literature research was carried out to compare topical pharmacotherapy (5-FU or IFN or MMC) to surgical excision regarding clinical success (tumor resolution), recurrence and complications in patients undergoing treatment for OSSN. From 7859 records, 7 articles were included in the qualitative and 4 in the quantitative synthesis. The outcomes of surgical excision and topical pharmacotherapy were comparable in the included articles. There were no significant differences between surgical excision and topical pharmacotherapy regarding the clinical success [odds ratio (OR): 0.785; confidence interval (CI): 0.130-4.736, P = 0.792)] and tumor recurrence (OR: 0.746; CI: 0.213-2.609; P = 0.646). The most common side effect of the different therapeutic options was dry eye. The highest rate of dry eye symptoms was reported after surgical excision (in 59%). Topical pharmacotherapy with all the 3 agents is as effective and well-tolerable as surgical excision in terms of tumor resolution, recurrence rate and side effects in all OSSN patients suggesting similar long-term clinical benefits.

Amniotic Membrane Grafting for Ocular Surface Inflammation Following Topical Interferon Alpha 2b Therapy.

We describe a rare case of a 58-year-old female with ocular surface squamous neoplasia (OSSN) in her left eye. She was treated for 12 months with topical interferon alpha-2b (IFNα-2b) eye drops and OSSN resolved completely. She presented with a whitish elevated lesion involving the cornea, limbus, and conjunctival surface after discontinuation of topical IFNα-2b. Excision biopsy along with amniotic membrane grafting was done to stabilize the ocular surface. Histopathological evaluation of the excised tissue revealed ocular surface inflammation with no evidence of malignancy.