Local ocular safety of the subconjunctival injection of cetuximab in rabbits.

BACKGROUND: To evaluate the safety of different doses of subconjunctival cetuximab in rabbits. METHODS: After general anesthesia rabbits received a subconjunctival injection of 2.5 mg in 0.5 ml, 5 mg in 1 ml, and 10 mg in 2 ml of cetuximab in their right eyes (two rabbits in each group). A similar volume of normal saline solution was injected subconjunctivally in the left eyes. The histopathologic changes were evaluated after enucleation with the aid of H&E staining. RESULTS: No significant difference were observed between the treated and control eyes in terms of conjunctival inflammation, goblet cell density, or limbal blood vessel density for all administered doses of cetuximab. CONCLUSION: Subconjunctival injection of cetuximab with the administrated doses in rabbit eyes are safe.

Association of Conjunctival Dysplasia (Squamous Intraepithelial Neoplasia) with Melanosis (Microscopic Non- Proliferative Melanin Pigmentation).

PURPOSE: To determine the association between conjunctival epithelial dysplasia (squamous intraepithelial neoplasia) and its melanosis (microscopic non-proliferative melanin pigmentation) in conjunctival biopsies. METHODS: In this retrospective case series, histopathological slides from all conjunctival biopsies obtained in Khalil Hospital affiliated with Shiraz University of Medical Sciences for a period of 6 years (April 2009-July 2015) were reviewed. After considering the exclusion criteria (non-melanotic pigmentation, melanocytic proliferations, and squamous cell carcinoma), conjunctival biopsies were divided histopathologically into two groups of dysplastic and non-dysplastic. Then, the slides were reviewed by one ophthalmopathologists and one general pathologist. Melanin pigmentation was recorded in both groups as 0, 1+, 2+, and 3+. The data were analyzed, and the groups were compared. RESULTS: Overall, 685 cases with a mean age of 47.78 (±17.74) years were included in this study. Dysplastic and non-dysplastic groups comprised 135 (19.7%) and 550 (80.3%) specimens, respectively. Seventy-six percent (76%) of the specimens in the dysplastic group versus 40% in the non-dysplastic group had melanosis (P = 0.001). However, the degree of dysplasia (1+, 2+, and 3+) was not statistically correlated with the degree of melanosis (1+, 2+, and 3+) (P = 0.393). CONCLUSION: Our results demonstrated that melanosis is a common finding in conjunctival epithelial dysplasia and might indicate an association with conjunctival epithelial dysplasia.

Safety of the subconjunctival injection of doxycycline in rabbits.

Purpose: To evaluate the safety of subconjunctival injection of doxycycline in rabbit eyes. Methods: Eight white New Zealand rabbits were selected. Different concentrations of 250 micrograms (µg), 500 µg, 1000 µg, and 2000 µg in 0.1 ml were prepared for subconjunctival injection. Each concentration was injected into the two eyes of each rabbit. For each dose, dextrose was injected in one contralateral eye and the other fellow eye remained non-injected. All rabbits underwent ocular examination in the 1st, 3rd, and 30th day after injection. The rabbits were sacrificed 30 days after injections and the histopathological examination was performed. Results: No obvious change was detected in all four groups from the 1st day to the 3rd day after injection in terms of tearing, hyperaemia, and chemosis. There was no visible sign of inflammation or necrosis, and also no histological change in both clinical and histopathological examinations. Conclusion: Subconjunctival injection of doxycycline with different dosages of 250 to 2000 ug in 0.1cc in rabbit eyes was safe and no clinical or histological changes were observed after one month.

Comparison of toluidine blue 1% staining patterns in cytopathologically confirmed ocular surface squamous neoplasias and in non-neoplastic lesions.

PURPOSE: To evaluate the role of toluidine blue (TB) staining patterns in diagnosis of ocular surface squamous neoplasia (OSSN) in comparison to that of impression cytology. METHODS: TB 1% dye was applied to different ocular surface lesions, followed by impression cytology (IC). Dye distribution, intensity, and pattern of uptake by the lesion were scored and total score ≥5 was considered "positive TB staining". The TB results were then compared with those using IC to determine the presence of cellular atypia. RESULTS: The study enrolled 88 eyes of 82 patients. IC demonstrated cellular atypia in 50 (56.8%) cases. Forty-three of 45 "TB-positive" eyes (95.51%) had cellular atypia on IC (p < 0.001). Sensitivity and specificity of TB in identifying OSSN were 86% and 94.74%, respectively, with positive and negative predictive values of 95.56% and 83.72%. TB staining intensity of dark blue and/or mixed types and stippled pattern of TB staining were strongly correlated with dysplastic changes in IC (P ˂ 0.001). TB staining distribution whether in form of diffuse, patchy or scattered eyes with atypia did not significantly differ from those without atypia in IC (P = 0.172). CONCLUSION: The sensitivity and specificity of TB vital dye in diagnosing OSSN can be increased by focusing on color intensity and a stippled pattern.

Impression Cytology in a Series of Clinically Diagnosed Ocular Surface Melanocytic Lesions.

PURPOSE: To report impression cytology (IC) results of clinically diagnosed ocular surface melanocytic lesions. METHODS: Ten patients with a clinical diagnosis of an ocular surface melanocytic lesion underwent IC using cellulose acetate strips and Periodic acid Schiff-Papanicolaou staining. Excisional biopsy of lesions was performed in case of observing atypical cells on IC or at the patient's request, and excised specimens were subjected to histopathological analysis. Agreement between clinical diagnoses and IC results and between IC results and histopathology were evaluated. RESULTS: Clinical diagnoses were nevi in 6, primary acquired melanosis (PAM) with atypia/melanoma in 2, and atypical nevus versus pigmented conjunctival intraepithelial neoplasia (CIN) in 2 cases. IC results were suggestive of a benign nevus in 7, PAM with atypia/melanoma in 2 and CIN versus an atypical epithelioid type melanocytic lesion in 1 case. IC results were consistent with the clinical diagnoses in 9 cases (Cohen's kappa index of 0.83) and excluded CIN in 1. Histopathology in 6 cases disclosed benign melanonevus in 3, malignant melanoma in the context of PAM with atypia in 2, and CIN in 1 case. Histologic results were well correlated with the IC features (Cohen's kappa index of 0.74). CONCLUSION: By demonstrating typical cytomorphological features of ocular superficial layers IC diagnosed the true nature of melanocytic ocular surface lesions in the majority of cases. Although IC does not substitute histopathology, given the high correlation between IC results and histopathology, it can be of great assistance in diagnosis and management of ocular surface melanocytic lesions.

Conjunctival Lesions; a Histopathologic Review in Fars Province, Iran.

PURPOSE: To determine the prevalence of various types of conjunctival lesions, at a tertiary ophthalmic center in Fars Province, South of Iran. METHODS: Histopathologic slides and medical records of conjunctival lesions submitted to the pathology department of Khalili Hospital, Shiraz, Iran were reviewed from April, 2009 to July, 2013. The histopathologic diagnoses were categorized into benign, pre-malignant, and malignant lesions. The prevalence of various types of conjunctival lesions was calculated. RESULTS: Histologic sections of 631 conjunctival lesions were reviewed. Benign lesions were most prevalent (81.8%), followed by premalignant (10.8%) and malignant (7.4%) lesions. Pterygia were the most common benign lesions (69.2%), intraepithelial dysplasia constituted most cases of premalignant lesions (94.1%), and squamous cell carcinoma was the most frequent malignant lesion (93.6%). Benign lesions were the most common type of lesions in all age groups, however the prevalence of malignant lesions increased significantly with age (P < 0.001). CONCLUSION: Benign lesions were the most common conjunctival lesions with pterygia on top of the list, while intraepithelial neoplasia and squamous cell carcinoma were the most common premalignant and malignant lesions, respectively. Conjunctival malignant lesions were more prevalent with older age.

Allergic Conjunctival Granuloma Presenting the Splendore-Hoeppli Phenomenon; Report of Two Cases and Review of Literature.

To report two cases of bilateral conjunctival granuloma with histopathological features of the Splendore-Hoeppli phenomenon and review of the literature. Two female patients, one with a history of pulmonary eosinophilic infiltration and another with a history of vernal keratoconjunctivitis, presented with bilateral cream to yellow colored nodules in the superior bulbar conjunctiva. Histopathologic examination revealed characteristic features of the Splendore-Hoeppli phenomenon manifesting as zones of amorphous eosinophilic material surrounded by aggregations of epithelioid histiocytes, giant cells, eosinophils and lymphoplasmacytic infiltrates. No evidence of infectious organisms was found. Our report adds to non-infectious cases of conjunctival Splendore-Hoeppli phenomenon. Previous history of allergic disorders may have contributed to the occurrence of this entity.

Synthetic Fiber "Teddy Bear" Conjunctival Granuloma; a Case Report.

PURPOSE: To report the clinicopathologic features of a case of conjunctival synthetic fiber granuloma. CASE REPORT: A 6-year-old girl presented with a slow-growing red nodule in the right inferior conjunctival sac with no history of surgery or trauma. Histopathological examination revealed foreign body type granulomatous inflammation around birefringent fibers of variable colors consistent with synthetic fiber granuloma. CONCLUSION: This is the first case report of synthetic fiber (teddy bear) conjunctival granuloma from Iran. Despite its scarcity, ophthalmologists should consider this type of granuloma in the differential diagnoses of childhood conjunctival lesions especially when the lesion is unilateral and inferior.