Intraocular Neoplasia Research Articles

A comprehensive overview of diagnosis, imaging and treatment of vitreoretinal lymphoma.

Vitreoretinal lymphoma (VRL) is a rare B-cell intraocular neoplasia characterized by poor long-term prognosis and lack of effective therapies. It mainly involves the vitreous humor, the retina, and the retinal pigment epithelium (RPE), although anterior segment involvement can occur. VRL is classified as a lymphoma of immune privileged sites, along with testis lymphoma and primary central nervous system lymphoma (PCNSL). VRL and PCNSL are strictly connected indeed: 80% of VRL develop PCNSL, while 20% of patients with PCNSL present VRL during natural history of lymphoma. Due to the lack of worldwide consensus about diagnosis, therapy, and follow-up timing, VRL represents one of the most challenging ocular affections.VRL commonly masquerades as a posterior uveitis, and misdiagnosis often occurs because of partial response to topical steroids. Gold standard for diagnosis is cytological analysis of vitreous humor. However, this technique lacks sensitivity and supplemental molecular analyses can improve the diagnostic process. Multimodal imaging allows ophthalmologists to empower their clinical suspicion and a comprehensive examination can highlight typical features of VRL and justify further invasive procedures.There is no consensus about VRL therapy, and none of the therapeutical scheme has demonstrated to prevent cerebral involvement and improve patient's overall survival. Intravitreal injections of chemotherapeutics drugs, ocular radiation therapy and systemic chemotherapy can be considered in the treatment of VRL. Once cerebral involvement occurs, systemic chemotherapy must be included in the treatment as a life-saving therapy. Further multicentric studies are required to find out the best treatment of patients with VRL.

Ocular Brachytherapy (Interventional Radiotherapy): Preserving the Vision

Uveal melanoma represents the most common intraocular neoplasia among adults. Brachytherapy (interventional radiotherapy; IRT) has a great advantage, when compared with enucleation, both in terms of organ and function sparing. The Collaborative Ocular Melanoma Study introduced into clinical practice a standardised procedure that allowed the equivalence of IRT with enucleation in terms of overall survival to be demonstrated. IRT is carried out by placing a plaque in direct contact with the sclera under the uveal melanoma. Several radioactive sources may be used, including 106-ruthenium, 125-iodine, 103-palladium and 90-strontium. It is a multidisciplinary procedure requiring the collaboration of interventional radiation oncologists and ophthalmologists in the operating theatre and medical physicists for an accurate treatment time calculation. It also relies on ultrasound imaging to identify the lesion and verifiy the correct plaque placement. An emerging tool of paramount importance could be the use of artificial intelligence and predictive models to identify those patients at higher risk of developing late side-effects and therefore who may deserve preventive and supportive therapies.

Rare primary choroidal melanoma in a dog, with optic nerve infiltration

Intraocular melanocytic neoplasms are common in dogs. However, the choroidal location of these neoplasms and their infiltration into the optic nerve are unusual. This paper reports a case of primary choroidal melanoma in a 12-year-old male Dachshund. On the first examination, the animal presented left eye blepharospasm, protrusion of the nictitating membrane, conjunctival hyperemia, moderate congestion, hyphema, and intraocular hypertension. Opacity hindered the performance of fundoscopy in the affected eye. The ocular ultrasound examination revealed a cupuliform mass in the choroid. Due to suspected intraocular neoplasia, an exenteration was performed. Histopathological examination revealed primary choroidal melanoma with scleral and optic nerve invasion.

Retrospective Study of Long-Term Outcome of Phacoemulsification in 22 Feline Eyes with Presumed Congenital/Juvenile Cataracts (2007–2020)

The objective of this study was to determine the complication risk and prevalence after phacoemulsification in cats with presumed congenital/inherited cataracts. Twelve client-owned cats were included in the study. This retrospective study spanned 13 yr and involved 22 eyes. The median age at the time of surgery was 15 mo (range: 4.5-168 mo of age). Recorded complications were 3 eyes developed postoperative ocular hypertension, 1 eye developed glaucoma, 7 eyes developed feline herpes virus-1 signs, and 7 eyes developed postoperative uveitis >2 wk after surgery. No eyes had developed intraocular sarcomas at the time of their last exam. All eyes remained visual at last follow-up (range: 0.5-121 mo). Success was defined as a comfortable and visual eye without intraocular neoplasia, glaucoma, a partial or complete retinal detachment, or uveitis that occurred >2 wk after surgery or persisted longer than 2 wk. Twenty-one out of 22 eyes had a successful outcome. In this study, cats with presumed congenital/juvenile cataracts who underwent phacoemulsification had an excellent outcome.

Retrospective evaluation of canine primary, multicentric, and metastatic intraocular neoplasia.

To provide an updated characterization of the prevalence of primary, multicentric, and metastatic intraocular tumors in the canine patient. Medical records databases from 4 veterinary referral hospitals were reviewed from 1999 to present to identify dogs with a diagnosis of intraocular neoplasia histopathologically confirmed following enucleation or necropsy. One hundred seventy-two dogs with 173 intraocular neoplasms met the inclusion criteria. Primary intraocular neoplasms were the most common tumors in the study (128); the two most common types were melanocytic neoplasia (90), followed by iridociliary neoplasia (33). There were 28 cases of intraocular involvement secondary to round cell neoplasia, with 18 cases of lymphoma, seven histiocytic sarcomas, and three undifferentiated round cell neoplasms. There were 17 cases of metastatic intraocular neoplasia, with hemangiosarcoma being the most common (9). The majority of intraocular tumors in dogs arise from the ocular tissues. However, the eye may also be involved in patients with multicentric neoplasia, and, less commonly, as a site for metastatic disease. Ocular screening for patients with multicentric neoplasia should be considered during staging, and ocular signs should be viewed with suspicion in dogs with neoplasia in other sites.

Glioma ocular em cão: Relato de caso

The objective is to report the case of a Transmontano Mastiff dog, eight year old intact male, 88 kg, with history of visual loss, diffuse corneal edema and secondary glaucoma. The ocular ultrasound examination revealed a hyperechoic structure located in the peripapillary region of the optic nerve, showing an image compatible with intraocular neoplasia. The animal was submitted to the enucleation procedure and anatomopathological analysis of the affected eye was performed. Histological examination revealed glioma of the optic nerve, considering that neoplasms that affect the retina and optic nerve are rarely described in veterinary medicine, as the case presented.

Causes, outcomes, and owner satisfaction of dogs undergoing enucleation with orbital implant placement.

To describe clinical and histopathologic pre-operative diagnoses as well as associated post-operative complications following orbital silicone implantation in dogs undergoing enucleation and evaluate owner satisfaction. One hundred and eighty-six dogs who underwent enucleation with orbital implant. Medical records from dogs that underwent enucleation with orbital implant performed at Virginia-Maryland Veterinary Teaching Hospital between 2007 and 2019 were reviewed. Owners were surveyed via telephone regarding client satisfaction. Enucleation followed by orbital implant placement occurred in 215 eyes of 186 dogs. The most common pre-operative diagnoses were glaucoma (68.8%), uveitis (17.7%), cataracts (15.8%), intraocular neoplasia (13.0%), and lens luxation (10.7%). The most common histopathologic diagnoses were retinal degeneration (46.5%), uveitis (39.5%), cataract (29.8%), retinal detachment (27.4%), and secondary glaucoma (26.5%). Fourteen eyes (6.5%) from ten dogs had post-operative complications reported including orbit cellulitis (n=11), implant migration (n=1), and implant extrusion (n=1). Five of these dogs (50%) had concurrent diabetes mellitus. Median complication time from surgery was 41days (range: 11-541days). Ninety-five owner survey responses were completed with a median time of 6.3years following surgery. Most owners, 85.3% (n=81), were satisfied with the post-operative outcome. Enucleation with implantation of an orbital implant is a viable and safe method for irreversibly blind eyes. Diabetes mellitus may be a risk factor for the development of post-operative complications. Intraocular neoplasia was not associated with development of post-operative complications. Results of this study indicated high owner satisfaction rates for improving cosmetic appearance after enucleation in dogs.

Iridociliary cysts masquerading as neoplasia in cats: a morphologic review of 14 cases.

To report 14 neoplasia-free feline eyes enucleated for suspected intraocular neoplasia containing only iridociliary cysts. To analyze clinical findings that may have led veterinarians to suspect neoplasia in these globes. The archives at the Comparative Ocular Pathology Laboratory of Wisconsin (COPLOW) were searched to identify neoplasia-free feline globes enucleated for suspected neoplasia. Clinical data were obtained from medical records, veterinarian surveys, and COPLOW submission forms. All samples were examined grossly and histologically. All eyes were free of neoplasia and contained one or more iridociliary cysts. Nine of 14 globes were enucleated by or based on the recommendation of a board-certified veterinary ophthalmologist. In eight of 14 cases, the submitting clinician listed melanoma as the only suspected diagnosis; in six of 14 cases, 'tumor' or 'mass' was listed. Clinical examination revealed a darkly pigmented intraocular mass in 11 of 14 cases. The mass was clinically perceived to be within the iris in seven of 14 cases. When examined histologically, 11 of 14 eyes contained multiple cysts, 13 of 14 contained multiloculated cysts, eight of 14 had a hyperplastic iris pigmented epithelium or cysts with thick black walls, and five of 14 had cysts prolapsed into the anterior chamber. Although most iridociliary cysts in cats are easily diagnosed on clinical examination, a subset may be mistaken for neoplasia. In cases of suspected iris melanoma, iridociliary cysts should be considered as a differential diagnosis, especially if a mass appears to emanate from behind the iris, dyscoria is present, or if similar changes are noted in the contralateral eye.

Immunohistochemistry of apoptosis-related proteins in retinoblastoma

Retinoblastoma is the most common intraocular malignant neoplasia during childhood and results from the partial or total inactivity of the retinoblastoma protein (pRb). In the absence of pRb, the E2F transcription factors increase the levels of cell cycle proteins as well as some pro-apoptotic proteins. We intended to study the immunohistochemistry profile of apoptotic-related proteins in retinoblastoma. We also evaluated the association between the expression of apoptotic protein and stage of tumor or survivor after a 5year follow up. Apoptosis-related proteins (Apaf-1, Bak, Bax, Bcl-2, Bcl-xL, Bim-long, MDM2, p53, pro-caspase-3, PUMA, Smac/DIABLO and cleaved caspase-3) were evaluated using immunohistochemistry on tissue microarrays which contained samples of retinoblastoma tumors taken from ninety-three patients without any treatment previous to surgery. The immunohistochemistry reactions were evaluated using an optical microscope as well as the ACIS III® platform. The pro-apoptotic proteins (APAF-1, Bax, p53, PUMA, Smac/DIABLO) were more frequently expressed than the anti-apoptotic proteins (Bcl-2, Bcl-xL and MDM2). The protein Bcl-xL had a negative correlation with cleaved caspase-3, a marker of cell apoptosis. Bcl-xL may be implicated in an apoptosis block.

Zur Epidemiologie des felinen Glaukoms

Objective: The aim of this retrospective study was to investigate the epidemiology and the risk factors of feline glaucoma presented between 1990 and 2011. Methods: Detailed information was obtained from case records. Glaucoma was classified as congenital, primary, or secondary. Data was evaluated for breed, gender, age at presentation, intraocular pressure, character of glaucoma, as well as etiology of secondary glaucoma. Results: A total of 124 cats with glaucoma were diagnosed between 1990 and 2011, 114 of which had secondary glaucoma 5 primary, and 2 congenital glaucomas. Three end-stage glaucomas could not be classified. The mean age at diagnosis was 9.7 ± 3.1 years, with a range between 30 days and 24 years. In ten different breeds the overall female:male ratio in all 124 cases was 1:1,8 (44 female and 80 male cats). The most common risk factors for development of secondary glaucoma were anterior uveitis (58.3%), intraocular neoplasia (17,1%), and lens luxation (7%). In 45 cats with secondary glaucoma the cause for uveitis was recorded: idiopathic (35.7%), Toxoplasma gondii (31.3%), trauma (22.2%), corona virus infection (8.9%), and feline leukemia virus infection (1.9%). Seventeen of the 20 cats with intraocular neoplasia had iris melanoma, and one each had a ciliary body adenoma/adenocarcinoma, lymphoma and metastatic neoplasia from a distant site. Conclusion: Most glaucomas were unilateral and secondary to other eye conditions. Nine risk factors for secondary glaucoma were identified, with anterior uveitis, intraocular neoplasia and lens luxation being the most prevalent. This is in agreement with similar earlier studies. POAG appears to be the most common form of primary glaucoma in cats.

Comparison of ultrasonography and histologic examination for identification of ocular diseases of animals: 113 cases (2000–2010)

To compare ultrasonographic and histologic examination findings for eyes of animals with ocular diseases. Retrospective case series. 116 eyes of 113 animals examined at 2 facilities. Diseased eyes of animals were examined by means of ultrasonography, removed via enucleation or exenteration, then histologically examined. Ultrasonographic images and histopathologic slides were evaluated, and diseases of eyes were identified with each of those methods and allocated to various categories. For each disease category, agreement between results of ultrasonography and those of histologic examination was assessed via determination of κ statistic values. Tests had good agreement for identification of iris or ciliary body neoplasia. Overall, intraocular neoplasia was not detected via ultrasonography for only 2 of 31 eyes with histologically detected neoplasia. Hemorrhagic or inflammatory changes were misinterpreted as neoplasia for 8 of 37 (22%) eyes. Tests had moderate to acceptable agreement for identification of retinal detachment. Retinal detachment was not detected by means of ultrasonography for 14 of 38 (37%) eyes with that diagnosis determined via histologic examination at one of the facilities (primarily in eyes with intraocular hemorrhage); however, retinal detachment was not identified via histologic examination for 6 of 38 (16%) eyes with that diagnosis determined via ultrasonography at the other facility. Agreement between tests evaluated in this study was clinically satisfactory for identification of intraocular neoplasia. Typically, diseases were misdiagnosed via ultrasonography for eyes with poor image contrast. Because determination of ultrasonographic diagnoses of retinal detachment and intraocular neoplasm may be of prognostic importance, performance of additional ultrasonographic techniques may be indicated.

Intravitreal cidofovir injection for the management of chronic glaucoma in dogs

The objective of this retrospective study was to determine whether an intravitreal injection of 562.5 ug of cidofovir was effective in lowering the intraocular pressure (IOP) in chronically glaucomatous avisual canine eyes. This study reviews the medical records of 167 canine patients diagnosed with chronic glaucoma between 2006 and 2011. The criteria for study inclusion were patients with irreversibly avisual eyes that were refractory to medical management, without evidence of endophthalmitis or intraocular neoplasia as determined by historical, clinical, and/or ultrasonographic examination, who were treated with an intravitreal injection of cidofovir. Using only topical anesthesia for most patients, aqueouscentesis was followed by an intravitreal injection of 562.5 ug of cidofovir and 1 mg of subconjunctival triamcinolone. An initial recheck was performed 14 days following the injection. The mean IOP immediately prior to injection was 46 ± 13 mm Hg with a median of 47 mm Hg. At the initial recheck, the mean IOP was 10 ± 11 mm Hg with a median of 6 mm Hg. A common postinjection finding was mild intraocular inflammation, which was controlled in all cases with topical neopolydex solution. Post injection complications included corneal ulceration (2.4%) and endophthalmitis (2.4%). Phthisis bulbi was a common sequalae (70%). One injection of cidofovir was successful in lowering the IOP in 85% of cases (P < 0.0001); multiple injections raised the success rate to 97%. An intravitreal injection of cidofovir was found to be an effective method of lowering intraocular pressure to <20 mm Hg. While the common side effect of phthisis bulbi resulted in a less than optimal cosmetic result, patients subjectively benefited from enhanced comfort warranting consideration of this approach in the management of chronically glaucomatous avisual canine eyes.

Translational models of ocular disease

Animals provide indispensable models to translate basic mechanistic discoveries and realize their therapeutic potential in humans. Conversely, advances in human medicine often inform management of similar conditions in clinical veterinary medicine. In this paper, key experimental model species are introduced, with emphasis on genetic contributions of the mouse. Its role and those of larger animal models are described in common ocular research areas including intraocular neoplasia, corneal epithelial and stromal disease, cataract, uveitis, glaucoma, and retinal dystrophies. Emphasis is placed on those conditions shared by humans and domestic animals, with the intent of exploring how the study of comparable conditions in humans, domestic animals, and laboratory animals informs one another.

Expression of vascular endothelial growth factor receptor‐1 and ‐2 in normal and diseased canine eyes

To immunohistochemically evaluate expression of vascular endothelial growth factor receptor-1 (VEGFR1) and -2 (VEGFR2) in ocular tissue of healthy dogs and dogs affected with primary glaucoma, uveitic glaucoma, and intraocular neoplasia. Enucleated globes from five dogs with primary glaucoma, five dogs with uveitic glaucoma, six dogs with intraocular neoplasms and three ophthalmically normal control dogs. Ocular tissues were obtained from enucleated globes of clinical cases or immediately following euthanasia for control dogs. Tissue sections were stained immunohistochemically for VEGFR1 and VEGFR2 via standard techniques and vascular tissue was qualitatively evaluated. Vascular endothelial VEGFR1 and VEGFR2 expression patterns are reported for normal and diseased ocular tissues. In addition, VEGFR1 and VEGFR2 expression patterns are reported for all normal ocular tissues. A constitutive expression pattern was detected for VEGFR1 by ocular vascular endothelial cells as well as nonvascular cells in the cornea, uvea, lens, and retina. VEGFR2 demonstrated limited expression in normal ocular tissue, but was widely expressed in vascular endothelium of diseased eyes, particularly in pre-iridal fibrovascular membranes. The results of this study suggest a role for VEGF receptors in both physiologic and pathologic angiogenesis in canine ocular tissue. Manipulation of this pathway may be a rational consideration for therapeutic intervention in canine ocular disease exhibiting pathologic neovascularization.

Intraocular signet‐ring cell melanoma in a hamster (Cricetulus griseus)

A two-and-a-half year-old male Chinese hamster (Cricetulus griseus) was referred for evaluation of an intraorbital mass involving the right eye. Based on ophthalmic examination and ultrasonography, a diagnosis of intraocular neoplasia was made. Enucleation of the affected eye was performed. The mass was histologically diagnosed as a primary malignant intraocular signet-ring cell melanoma. No signs of recurrence were detected, and the hamster remained clinically healthy until it died 6 months after surgery. This case report attempts to contribute to the limited body of knowledge available in the literature on primary intraocular neoplasms in hamsters.

Aqueous humor vascular endothelial growth factor in dogs: association with intraocular disease and the development of pre‐iridal fibrovascular membrane

To examine the concentrations of vascular endothelial growth factor (VEGF) in aqueous humor of dogs with intraocular disease and to evaluate the association of aqueous humor VEGF with pre-iridal fibrovascular membrane (PIFM) formation. Two hundred and twenty six aqueous humor samples and 101 plasma samples were collected from 178 dogs with a variety of intraocular diseases (including cataract, primary glaucoma, uveitic glaucoma, aphakic/pseudophakic glaucoma, retinal detachment, lens luxation, and intraocular neoplasia), and aqueous humor was collected from 13 ophthalmically normal control dogs. Systemic disease status and administration of select medications were recorded. Aqueous and plasma VEGF was assayed via enzyme-linked immunosorbant assay validated for canine VEGF. Available histopathology samples were examined for the presence of PIFM. Where present, PIFMs were categorized as none, cellular, vascular or fibrous, and fibrovascular. Data were evaluated by mixed model anova, with application of Tukey-Kramer adjustment for multiple comparisons. There was no association between aqueous humor and plasma VEGF levels. Compared with normal controls, aqueous humor VEGF was significantly elevated for all intraocular diseases (P < 0.05) except for primary and diabetic cataracts. Systemic disease and administered medications had no significant effect on aqueous humor VEGF concentration. Compared to dogs without PIFM, aqueous humor VEGF was significantly higher in dogs with fibrovascular PIFM (P = 0.001), but not cellular (P = 0.1704) or fibrous/vascular PIFM (P = 0.0667). These findings confirm that VEGF is commonly elevated in aqueous humor of dogs with intraocular disease and likely plays a role in the causation or progression of a variety of intraocular disorders, including the development of PIFM.

Modified evisceration technique in a golden eagle (Aquila chrysaetos)

Two different modified techniques have been described for enucleation in raptors, including the transaural approach and the globe-collapsing procedure. This case report describes an alternative, modified evisceration procedure in a mature female Golden Eagle (Aquila chrysaetos). The advantages of this procedure are decreased anesthetic time, ease of procedure, decreased risk of excessive traction of the optic nerve, decreased intraoperative orbital trauma, and preservation of the natural symmetry of the head. The major disadvantage of this procedure is that it does not allow complete histologic examination of the globe. Patients with intraocular infection or neoplasia, or significant orbital disease may be poor candidates for this technique.

Epidemiology of canine glaucoma presented to University of Zurich from 1995 to 2009. Part 2: secondary glaucoma (217 cases)

To investigate the epidemiology of canine secondary glaucomas in the cases presented to the University of Zurich, Vetsuisse Faculty (UZH) from 1995 to 2009 focusing on possible risk factors for developing secondary glaucoma in this population of dogs. Information was obtained from the computer database of patients examined by members of the UZH Ophthalmology Service, between January 1995 and August 2009. Secondary glaucoma was diagnosed based on the presence of antecedent eye conditions. The data was evaluated for breed, gender, age at presentation, and for antecedent eye conditions known to cause glaucoma including anterior uveitis of unknown cause (AU), lens luxation (LL), intraocular surgery (SX), intraocular neoplasia (IN), unspecified trauma to the globe (T), ocular melanosis (OM), hypermature cataract (PY), hyphema (HY), and six other less frequent conditions. A total of 217 dogs were diagnosed with secondary glaucoma from 1995 to 2009. The age of the dogs with secondary glaucoma ranged between 88 days and 19 years (mean 7.7 ± 3.6 years). Data suggested a predisposition for secondary glaucoma in the Cairn Terrier and the Jack Russell Terrier breeds from 2004 to 2009. Common causes of secondary glaucoma from 1995 to 2009 were AU (23.0%), LL (22.6%), SX (13.4%), IN (10.6%), T (8.3%), OM and PY (both 6.9%) and HY (3.23%). The report presents the epidemiology of secondary glaucomas presented to UZH from 1995 to 2009. Fourteen risk factors were recorded for secondary glaucoma. This is the first paper documenting OM in the Swiss Cairn Terrier dog population.

Feline Glaucomas

Cats are usually presented at a very late stage in the course of glaucoma when the eye is already blind. Secondary glaucoma because of another underlying ocular lesion is the most common form of glaucoma in the cat and is frequently associated with chronic anterior uveitis or intraocular neoplasia. Chronic stages of glaucoma in the cat are characterized by buphthalmus, anterior lens luxation, and exposure keratitis secondary to the enlarged globe. Ophthalmoscopic signs of glaucomatous retinal degeneration are only noticed in very advanced stages. Treatment of glaucoma in cats is usually aimed to keep the eye comfortable and within a normal intraocular pressure range. However, many antiglaucoma medications that are successfully used in humans and dogs are not very well tolerated by cats and, therefore, the selection of recommended drugs is limited in this species.

Choroidal Melanoma in a Dog

A 7-year-old intact female golden Retriever was referred for evaluation of an intraorbital mass of the left eye. Based on ophthalmoscopy, ultrasonography and magnetic resonance imaging (MRI), the tentative diagnosis was made as an intraocular neoplasia, especially choroidal melanoma. The orbital exenteration of the affected eye was performed. The mass was histologically diagnosed as malignant choroidal melanoma. No signs of recurrence and metastasis were detected by thoracic radiographs, blood examinations and MR images, and the dog was clinically healthy for 23 months after operation.