Novel Meibomian Gland and Tarsal Conjunctival Changes Associated with Trastuzumab, Pertuzumab, and Anastrozole Treatment for Metastatic HER2 Positive Breast Cancer: A Case Report and Literature Review.

The aim of the study was to report a case of severe meibomian gland dysfunction (MGD) and conjunctival changes associated with trastuzumab, pertuzumab, and anastrozole therapy in a HER-2 positive breast cancer patient. A 57-year-old white woman was treated with trastuzumab and pertuzumab biological and anastrozole endocrine therapy for metastatic breast cancer for several months. She suffered from intense eye pain and foreign body sensation. On the ocular surface, severe MGD developed without corneal lesions. On the tarsal conjunctiva, circumscribed lesions evolved 6 months after receiving anticancer therapy. After biopsy, the histological assessment excluded metastasis or chalazion. The lesion consisted of subepithelial lymphocytic infiltrates surrounding lipid-laden CD68-positive macrophages. Besides the redundant lipid accumulation, no acute necrotic reaction was seen. Noncontact infrared meibography visualized ductal drop-out in the upper and lower lids, and functional tests confirmed severe MGD. During the 18-month follow-up, the patient received treatment for MGD and no new conjunctival lesions developed, subjective symptoms subsided, and ocular surface morphology remained unchanged. The novel HER2-inhibitor trastuzumab and pertuzumab biological therapy and anastrozole endocrine therapy were associated with the disruption of the ocular surface milieu. The new histological aspect of tarsal conjunctiva changes may give a hint to understand the potential underlying molecular mechanisms of anticancer therapy-associated severe MGD. Since anticancer therapies may substantially interfere with the ocular surface milieu, awareness of this side effect leads to improved care of oncology patients.

[Metastatic clear cell renal cell carcinoma: a potential mimicker of choroidal melanoma]. / Világossejtes vesesejtes karcinóma koroideális melanómát utánzó áttéte.

While metastases are the most common intraocular malignancies, ocular metastases of renal cell carcinoma are rare. The most frequent primary malignancy of the eye is uveal melanoma. The common ocular localization is the choroid in both cases. The clinical differentiation of choroidal metastasis from renal cell carcinoma and choroidal melanoma malignum is a diagnostic challenge for the ophthalmologist. We present two cases where renal cell carcinoma had metastasized to the choroid. Enucleation was performed in a 61- and a 71-year-old male patient with suspected advanced choroidal malignant melanoma following biomicroscopic and B-scan ultrasonography examination. Histopathological examination confirmed clear-cell renal cell carcinoma in both cases. The clinical and ultrasonographic appearance of clear-cell renal cell carcinoma metastasis may mimic choroidal malignant melanoma, and may only be suspected if a primary renal cell carcinoma is already established.

Non-malignant conjunctival epithelial masses with ocular surface squamous neoplasia-like optical coherence tomography features.

PURPOSE: To observe and describe the anterior segment optical coherence tomography features of limbally localised non-malignant epithelial mass lesions METHODS: Thirteen patients (age: 66.9 ± 16.3 years) with conjunctival mass suggesting ocular surface squamous neoplasia with biomicroscopic examination were imaged using anterior segment ocular coherence tomography (anterior segment optical coherence tomography)/Cirrus HD-OCT, Model 4000, Carl Zeiss Meditec, Inc., Dublin, CA, and Spectralis HRA + OCT system, Heidelberg Engineering, Vista, CA/. Cases with ocular surface squamous neoplasia-like anterior segment optical coherence tomography (hyperreflective, thickened epithelium and an abrupt transition from normal to abnormal) were included in the study. Maximal thickness of the epithelium was measured. Histological diagnosis was gained from an excisional or incisional biopsy or impression cytology specimens. RESULTS: In six patients (age: 68.5 ± 15.4 years) with ocular surface squamous neoplasia-like anterior segment optical coherence tomography features, the histological diagnosis was other than ocular surface squamous neoplasia (papilloma, parakeratosis and a keratotic plaque with mild dysplasia), and ocular surface squamous neoplasia in seven cases (age: 65.6 ± 18.0 years). The maximal epithelial thickness was between 250 and 859 µm in non-ocular surface squamous neoplasia cases and between 252 and 596 µm in ocular surface squamous neoplasia cases. CONCLUSION: Non-malignant epithelial lesions can mimic ocular surface squamous neoplasia on anterior segment optical coherence tomography.

Changing trends in penetrating keratoplasty indications at a tertiary eye care center in Budapest, Hungary between 2006 and 2017.

AIM: To analyze the changing trends in penetrating keratoplasty (PKP) indications. METHODS: This retrospective study included all patients with PKP between 2006 and 2017. Patients were classified using histological diagnoses. Our groups were as the following: pseudophakic or aphakic bullous keratopathy, regraft, acute necrotizing and ulcerative keratitis, keratoconus, Fuchs' dystrophy, corneal dystrophy other than Fuchs', corneal scar, other diagnoses and failed endothelial keratoplasty graft. Additionally, two different time-periods (2006-2012 and 2013-2017) were analysed. RESULTS: Totally 1721 histological analyses of 1214 patients were available for review. The diagnoses were pseudophakic or aphakic bullous keratopathy in 487 (28.3%), regraft in 443 (25.7%), acute necrotizing and ulcerative keratitis in 313 (18.2%), corneal scar in 153 (8.9%), keratoconus in 140 (8.1%). Fuchs' dystrophy in 61 (3.5%), corneal dystrophy other than Fuchs' in 46 (2.7%), other diagnoses in 44 (2.6%) and failed endothelial keratoplasty graft in 34 (2.0%) cases. From the first to the second analysed time-period, incidence of acute necrotizing and ulcerative keratitis, corneal scar, Fuchs' dystrophy increased (P≤0.032 for all) and incidence of keratoconus significantly decreased (P=0.015). CONCLUSION: Pseudophakic or aphakic bullous keratopathy is the leading indication for PKP, followed by regraft and acute necrotizing and ulcerative keratitis.

Clinicopathological Review of 547 Bulbar Enucleations in Hungary (2006-2017).

PURPOSE: To analyse current clinicopathological enucleation indications in a large third-referral centre in a developed country (Hungary) over a period of 12 years. METHODS: Retrospective review was performed on 547 enucleated eyes of 543 patients (48.6% males, age 52.7 ± 24.5 years) who were operated on between 2006 and 2017 at the Department of Ophthalmology of Semmelweis University, in Budapest, Hungary. For each subject, clinicopathological data, including patient demographics, indications for enucleation, B-scan ultrasound reports, operative details, and histopathological analyses, were reviewed. Primary enucleation indications were classified into trauma, tumours, systemic diseases, surgical diseases, infections or inflammations, miscellaneous diseases, and unclassifiable groups. Clinical immediate enucleation indications were classified as tumours, atrophia or phthisis bulbi, infection or inflammation, painful blind eye due to glaucoma, acute trauma, threatening or spontaneous perforation, cosmetic causes, and expulsive bleeding. RESULTS: The most common primary enucleation indications were tumours (47.3%), trauma (16.8%), surgical diseases (15.7%), infection or inflammation (11.6%), systemic diseases (5.1%), miscellaneous diseases (2.0%), and unclassifiable diseases (1.5%). Clinical immediate enucleation indications were tumours (46.1%), atrophia or phthisis bulbi (18.5%), infection or inflammation (18.5%), painful blind eye due to glaucoma (11.2%), acute trauma (3.7%), threatening or spontaneous perforation (1.3%), cosmetic reasons (0.5%), and expulsive bleeding (0.4%). CONCLUSIONS: Intraocular tumours represent the most common clinicopathological indication for ocular enucleation in our study population. Following ocular trauma and systemic diseases, the rate of enucleation decreased in the last decade, compared to those previously reported in other developed countries. However, changes were not observed for surgical diseases, infectious and inflammatory causes, or for miscellaneous and unclassified diseases. Orbital implant financing should be increased to ensure better postoperative aesthetic rehabilitation, following enucleation in Hungary.

[Ocular manifestations and management of Fusarium and Sarocladium infections]. / Fusarium és Sarocladium okozta fertozések szemészeti vonatkozásai és azok kezelése.

Since 2017, the nomenclature of Fusarium, Acremonium and Sarocladium species have changed, as these morphologically homogeneous, but phylogenetically heterogeneous species and species complexes may be differentiated using MALDI-TOF MS examination, analyzing nucleotic sequences. This resulted in taxonomical changes. We summarize the clinical course, diagnostic and therapeutic options of keratitis caused by Fusarium and Sarocladium. The challenge of Fusarium and Sarocladium keratitis management for an ophthalmologist lies in delayed diagnosis and therapy, fulminant progression and penetration of the Descemet's membrane, restricted availability, poor penetration of antifungal agents and therapy resistance. The diagnosis is based on the clinical history of corneal trauma or contact lens wear, PCR and MALDI-TOF MS, confocal microscopic examination, microbiological culture and light-microscopic analysis of corneal scrapings. As primary conservative treatment, 5% natamycin eye drops have to be used and with results of an antimycogram, topical 1% voriconazole or 0.15-0.25% amphotericin B, in some cases 0.02% polyhexamethylene-biguanide (PHMB) may be applied. Fusarium keratitis may benefit from additional 2 × 200 mg oral voriconazole treatment, daily. In therapy resistant cases, early, large diameter penetrating keratoplasty (PKP) has to be performed, with complete removal of the infected area. With late diagnosis, delayed specific treatment and surgery, mycotic hyphae may penetrate the Descemet's membrane, leading to the loss of vision and enucleation in about every fourth patient. In our paper, we also present the heterogeneous clinical history of five Fusarium and Sarocladium keratitis cases. Orv Hetil. 2019; 160(1): 2-11.

[Corneal deposits in monoclonal gammopathy of undetermined significance. Review of the literature and case report]. / Szaruhártya-lerakódások bizonytalan jelentoségu monoklonális gammopathiában. Irodalmi áttekintés és esetbemutatás.

To summarize ophthalmological signs of monoclonal gammopathy of undetermined significance (MGUS) and to present a case report. Summary of the literature data and presentation of the history of a 46-year-old female patient. In MGUS, pathological, but non-malignant plasma cells produce abnormal monoclonal immunoglobulin. Its prevalence is 0.15%, but it increases with age. As yearly 1-2% of MGUS patients develop multiple myeloma, frequent hematological follow-up is necessary. Corneal opacifications in MGUS have been described in a few dozens of patients in the literature. These may be nummular or crystal-like, or even present with white or grey line-forming depositions in the stroma. They may be centrally or peripherally localized. In our patient, bilateral, branching, geographical corneal opacifications were detected predescemetally, that were progressing and reaching the optical centre during follow-up. With 0.15 best corrected visual acuity, penetrating keratoplasty was performed (postoperative best spectacle-corrected visual acuity 0.6). Masson trichrom staining of the explanted cornea verified protein deposition, immunhistochemistry identified kappa light chain immunglobulin deposition in the posterior stroma, surrounded with inflammatory cells. Serum electrophoresis and bone marrow biopsy of our patient proved MGUS, therefore, hematological follow-up is going on. In the case of progressive, atypical corneal opacification, the hematological diagnosis of monoclonal gammopathy must be excluded - monoclonal gammopathy of ocular significance -, as delay in proper diagnosis and treatment of the systemic disease may have devastating consequences. Orv Hetil. 2018; 159(39): 1575-1583.

[Ocular surface squamous neoplasia]. / Szemfelszíni laphám-neoplasia.

To summarize actual knowledge on epidemiology, etiology, pathology, clinical apparence and treatment of ocular surface squamous neoplasias. We summarize up-to-date literature on conjunctival intraepithelial neoplasia and invasive squamous cell carcinoma and present some own cases. Ocular surface squamous neoplasia is the most common malignant ocular surface tumor and the third most common ocular malignancy following malignant melanoma and lymphoma. In spite of its low malignant potential, in advanced stages it may reduce visual acuity significantly or even the eye globe has to be removed. In case of metastasis it may also be life-threatening. As local recurrences of ocular surface squamous neoplasias may occur, knowledge of intra- and postoperative adjuvant treatment options are indispensable and regular control examinations are necessary. Identification and adequate treatment of ocular surface squamous neoplasias are necessary in order to avoid its progression and to prevent recurrences. Orv Hetil. 2017; 158(51): 2011-2022.

Evaluation of lymphatic vessel dilatations by anterior segment swept-source optical coherence tomography: case report.

BACKGROUND: Conjunctival lymphangiectasia is a rare condition presumably caused by the obstruction of lymphatic channels or by an abnormal connection between conjunctival lymphatic and blood vessels. Diagnosis is based on clinical appearance and histology. We report a case of conjunctival lymphangiectasia in which anterior segment optical coherence tomography (OCT) was used to assist the diagnosis and the planning of the biopsy location. CASE PRESENTATION: A 31-year-old woman was referred with repeated episodes of conjunctival "hemorrhages" and chemosis with extended recovery periods over the last months. Other symptoms were dryness, redness, burning sensation and itching. Photo documentation, anterior segment OCT, ultrasound, computer tomography (CT) and magnetic resonance imaging (MRI) of the brain were performed. MRI revealed dilated atypical Virchow-Robin space (VRS). Conjunctival biopsy was taken and the location of the biopsy was selected based on OCT findings. Based on the clinical appearance we suspected the case to be conjunctival lymphangiectasia or lymphangioma. Histology and immunhistochemistry confirmed the diagnosis of conjunctival lymphangiectasia. CONCLUSIONS: Anterior segment OCT is a non-invasive tool, useful in the evaluation of conjunctival lesions and planning surgery.

Specificity of in vivo confocal cornea microscopy in Acanthamoeba keratitis.

PURPOSE: To report on the presence of 4 different structures visualized by confocal microscopy in patients whose clinical presentation suggested infection by Acanthamoeba. METHODS: Data and charts of 28 consecutive patients were analyzed in a retrospective study. Four types of structures were recognized by confocal microscopy performed with HRT II Rostock Cornea Module: trophozoites, double-walled cysts, signet rings, and bright spots. The 28 patients (mean age 30.8 years, range 17-61 years, 10 male, 18 female) were divided into 4 groups according to the diagnosis established later by microscopic examination of smear, culture, response to therapy, and the course of keratitis. The 4 groups were Acanthamoeba keratitis (AK), Acanthamoeba suspect (AK-suspect), bacterial keratitis (BK), and fungal keratitis (FK). RESULTS: The rate of patients in AK, AK-suspect, FK, and BK groups where bright spots were found were 100%, 100%, 40%, and 55%, respectively. The sensitivity of presence of bright spots in the in vivo confocal microscopy in Acanthamoeba keratitis was 100% (95% confidence interval [CI] 73.5% to 100.00%) and specificity was 50% (CI 24.7% to 75.4%). When cases where the only signs of Acanthamoeba were bright spots were excluded, and only those cases were counted where any of cysts, trophozoites, or signet rings were also found, the sensitivity was 67% (95% CI 34. 9% to 90.1%) and the specificity was 94% (95% CI 69.8% to 99.8%). CONCLUSIONS: The relatively high rate of bright spots in non-Acanthamoeba keratitis challenges the assumption that bright spots seen by confocal microscopy are a specific indication of Acanthamoeba keratitis.

Cbfa1/Runx2 expression in an ossifying basal cell carcinoma of the eyelid.

A case of basal cell carcinoma (BCC) with intratumoural bone formation affecting the eyelid of a 77-year-old lady is described. Bone formation in BCCs is an uncommon event. We revised the 23 cases described in the literature: most of them occurred on the face. The pathophysiological mechanism responsible for ossification in cutaneous lesions remains unclear. The bone often develops adjacent to, or within hair follicles. We evaluated the immunohistochemical expression in the present case of Cbfa1/Runx2, an early marker for osteoblastic progenitor cells. A well-developed lamellar bone with adipose bone marrow was observed both in the superficial stroma and intratumourally. Cbfa1/Runx2 was localised in the osteocytes of the heterotopic bone and in the keratin cysts of the BCC. The expression of Cbfa1/Runx2 in the present BCC suggests a possible role of this protein in the induction of the heterotopic bone.

Bilateral Retinoblastoma Presenting with Unilateral Phthisis.

Phthisis of the eye is an uncommon presenting sign of retinoblastoma. The authors report a case of bilateral retinoblastoma in a 14-month-old girl who presented with phthisis of the left eye. Enucleation of the painful left eye was performed. Spontaneously regressed, mostly calcified retinoblastoma was diagnosed. The patient underwent chemoreduction. Plaque radiotherapy and transpupillary thermotherapy were applied on the right side. Subsequent ophthalmoscopic examination revealed lesions showing "cottage-cheese" regression. Retinoblastoma should be suspected in any child presenting with phthisis bulbi of unknown origin and a detailed examination of the other eye should be performed.

Two cases of congenital simple hamartoma of the retinal pigment epithelium.

PURPOSE: Congenital simple hamartoma of the retinal pigment epithelium (CSHRPE) is a rare fundus condition. Two cases of CSHRPE are reported. METHODS: The clinical findings and biomicroscopy, fluorescein angiography, optical coherence tomography (OCT), and ultrasonography features differentiating this pigmented macular tumor from uveal melanoma or retinal pigment epithelium (RPE) anomalies and neoplasms are discussed. RESULTS: Two patients were observed with a pigmented macular lesion. Sharply demarcated transretinal lesions were seen in the macula of both patients, arising from the RPE. The periphery of the lesion in Case 1 was flat and black; the central portion was elevated and fibrotic with a central vitreous strand. A narrow crescent of RPE atrophy was noted temporally. Optical coherence tomography of both lesions showed the typical findings of CSHRPE: high reflectivity, irregular surface, abrupt borders, and full-thickness retinal shadowing. The decision was made to observe the lesions. During follow-up, the lesions remained unchanged. CONCLUSION: The unusual finding of CSHRPE associated with RPE atrophy makes the differentiation between CSHRPE and hyperplasia of the RPE even more difficult. Noninvasive OCT has a major role in the diagnosis of CSHRPE.

Orbital tumour as initial manifestation of acute myeloid leukemia: granulocytic sarcoma: case report.

We report orbital involvement as an initial manifestation of acute myeloid leukemia in a 57-year-old woman. The patient presented with painful proptosis and limited ocular motility. Orbital computed tomography revealed bilateral homogeneous masses. Orbital biopsy was performed on the right side; and histopathology disclosed a myelocytic tumour. Despite treatment using irradiation and chemotherapy, the patient died eleven months after presentation. There appear to be only a few previous reports of acute myeloid leukemia cases presenting with orbital involvement, and most cases occurred in children. This very rare condition has a poor survival prognosis, even with radiation treatment and chemotherapy.

Long-term exposure of the rabbit eye to silicone oil causes optic nerve atrophy.

A silicone oil endotamponade following vitrectomy has for decades been a standard method in human ophthalmology with a view to restoring a detached retina. However, severe functional deficiencies may remain after treatment. In adult rabbits, the injection of silicone oil into the eye-ball following vitrectomy resulted in a decrease of 89% in the number of myelinated optic nerve fibres after a survival time of 1 year (418,313+/-29,703 versus 45,620+/-23,905). Concomitantly, the cross-sectional area of the optic nerve was also reduced significantly (0.853+/-0.159 mm2 versus 0.355+/-0.107 mm2). The number of non-neuronal elements of the optic nerve remained virtually unchanged immediately behind the eye-ball and in the middle part of the nerve, whereas it increased significantly close to the optic chiasm (3040+/-433 versus 3888+/-403). Thus, destruction of the myelinated optic nerve fibres is likely to be responsible for the functional deficiencies observed after silicone oil implantation.

[Retrospective study of uveal melanoma]. / Uveális melanomák retrospektív vizsgálatának tapasztalatai.

PURPOSE: To report the results of a retrospective study carried out at the 1st Department of Ophthalmology of Semmelweis University, Budapest, among patients treated for ocular melanoma. Clinical data of the patients, histopathological characteristics of the tumours and follow-up results are reported. PATIENTS AND METHODS: Retrospective review of patients' charts, histopathological data and statistical analysis of collected data. RESULTS: From 120 patients treated by enucleation or exenteration for uveal melanoma, 22 had died by the end of the study. The medium survival after operation was 34.0+/-25.4 months, the majority of deaths occurred within three years following surgery. Statistically significant relationship was demonstrated between extraocular extension of the tumour and death, and between epithelioid cell tumours and death. Most large tumours involved the ciliary body, the prognosis of these tumours tended to be worse than for those infiltrating only the choroid, but the difference was not statistically significant. Uveal melanoma almost exclusively gives haematogenous metastases, liver metastases being the most frequent; rarely lung metastases are also reported. Since extraocular extension and epithelioid tumours carry a very poor prognosis, the possibility of providing adjuvant chemo-immunotherapy for patients harbouring these tumours should be entertained, even if liver metastases are not demonstrated at the time of diagnosis.

[Evaluation of color Doppler imaging of ophthalmic tumors based on histopathologic findings]. / Szemészeti daganatok színkódolt ultrahangvizsgálatának értékelése a szövettani eredmény tükrében.

PURPOSE: To examine retrospectively the diagnostic and differential diagnostic value of color Doppler imaging (CDI) in cases of suspected intraocular and orbital tumors. PATIENTS AND METHODS: Color Doppler examination (using Acuson 128, Philips-ATL UM-9, HDI 3000, 5000, Siemens Elegra, GE Logiq9) was performed in a total of 194 patients (177 intraocular, 17 orbital tumors). The results were compared to the clinical findings (routine examination, conventional ultrasound examination) and the results of angiography (FLAG, ICG). Furthermore, in 73 cases histopathology records were obtained for comparison. RESULTS: Signs of blood flow could be detected in 137 cases (71%); the Doppler spectrum was low resistance in the large majority (130) of these cases. In cases where histopathology records were available, 60 of the 73 (82%) showed good concordance between the CDI diagnosis and the pathological results. CDI gave false positive results in 3, and false negative findings in 10 cases; the latter occurred mainly in small iris or ciliary body tumors. CONCLUSIONS: Using CDI, blood flow is demonstrable in the majority of intraocular and orbital tumors, especially if the tumor diameter is larger than 3 mm. CDI flow detection, however, is less reliable for iris or ciliary body tumors.

Silicone oil in the subarachnoidal space--a possible route to the brain?

Using this case report, we sought evidence that silicone oil may infiltrate the subarachnoidal space. Vitrectomy combined with silicone oil implantation was performed on the right eye of a 72-year-old woman. The silicone oil was removed 2 months later, because the patient had developed elevated intraocular pressure. The blind and painful eye was subsequently enucleated. By light microscopy, presumed silicone oil bubbles were identified in the optic nerve and the subarachnoidal space of the enucleated eye. These vacuoles were examined by energy-dispersive X-ray analysis (EDAX). In addition, in the vacuoles, immunohistochemistry was used to test for the presence of CD 68-positive macrophages. Silicone oil infiltration sites in the optic nerve, in the central retinal artery, and in the subarachnoidal space were located by light microscopy and confirmed by EDAX. CD 68-positive macrophages were found in the silicone-filled vacuoles. Silicone oil used for endotamponade may infiltrate the optic nerve and even the subarachnoidal space. This supports the assumption that silicone oil, under special circumstances, may even migrate into the brain.

The role of ultraviolet-B in corneal healing following excimer laser in situ keratomileusis.

Corneal photoablation with the 193 nm argon fluoride excimer laser during photorefractive keratectomy (PRK) in high diopter range is frequently associated with subepithelial haze and consequent refractive regression due to avascular corneal wound healing. The wound healing response can be augmented by Ultraviolet-B (UV-B) exposure originating from sun or solarium. Clinically Laser in situ Keratomileusis (LASIK) even in high diopter range is associated with less subepithelial haze and regression than PRK. In an animal model, the morphologic changes of the rabbit cornea were evaluated following LASIK and secondary UV-B exposure. Light microscpic changes were found to be insignificant. Transmission electron microscopy (TEM) normal epithelium, epithelial adhesion structures and normal anterior stroma showed in the LASIK treated UV-B irradiated rabbit eyes. Around the peripheral LASIK cut, migrating keratocytes with pseudopodia were observed. Under the flap (160 microm depth) the overall stromal collagen structure was normal, some activated keratocytes and mild extracellular matrix formation within and around keratocytes were noted. Within activated keratocytes TEM showed prominent rough endoplasmic reticulum, Golgi apparatus, mitochondria and extracellular vacuoles, which showed resolution with time. These changes were much milder than in PRK treated-UV-B irradiated eyes. Secondary UV-B caused no long-term disturbance in corneal transparency in LASIK and UV-B treated rabbit eyes.