Eye Pathology Research Articles

Связь эксфолиативной глаукомы с дистрофическими и сосудистыми изменениями структур глаза и патологией сердечно-сосудистой системы

Связь эксфолиативной глаукомы с дистрофическими и сосудистыми изменениями структур глаза и патологией сердечно-сосудистой системы

Clinicopathologic review of pediatric enucleations during the last 50 years

To evaluate diagnoses leading to enucleations in the pediatric age group over time. All pathology reports of enucleation specimens at the University of California-San Francisco eye pathology laboratory from children (ages 0 to 18 years) from 1960 to 2008 were reviewed. The main outcome measures were the frequency of pediatric enucleation specimens in each diagnostic category as compared with total pathological laboratory volume over time, and the age and gender distribution of histopathological diagnostic categories over time. Specimens of 746 eyes from 729 pediatric patients were analyzed. Pediatric enucleated eyes constituted 2.7% of all specimens received at the pathology laboratory. The overall frequency of pediatric enucleation specimens did not change over time. Retinoblastoma specimens increased by a factor of 2.9 over time (p < 0.0001). The increase in retinoblastoma was offset by a decrease in nonretinoblastoma enucleations, which decreased by a factor of 3.8 between the 1960s and 2000s (p < 0.0001), driven by a decrease in enucleations caused by trauma (p < 0.0001). Beginning in the 1980s, pediatric enucleations caused by nonrhegmatogenous retinal detachment, nematode and non-nematode endophthalmitis, and congenital glaucoma decreased significantly. Retinoblastoma was the most common diagnosis overall (45%), in girls (60%), and in ages <5 years (78%). Trauma was the second most common diagnosis (32%) and the most common in boys (42%) and in children ages 6-12 (58%) and 13-18 (72%) years. A decrease in pediatric nonretinoblastoma enucleations was observed over time, possibly attributable to better diagnostic capabilities, surgical techniques, and public health interventions. The increase in retinoblastoma enucleations over time was likely due to the result of institutional referral bias.

Characterizing kidney and eye pathology of complement factor H deficient mice

Characterizing kidney and eye pathology of complement factor H deficient mice

Concurrent epizootic hyperinfections of sea lice (predominantly Caligus chiastos) and blood flukes ( Cardicola forsteri) in ranched Southern Bluefin tuna

Peaks in epizootics of sea lice (mostly Caligus chiastos) and blood flukes ( Cardicola forsteri) among Southern Bluefin tuna ( Thunnus maccoyii) appear to coincide with the onset of an increased mortality. The mortality event occurs 6–12 weeks after T. maccoyii have been transferred into static ranching pontoons from the wild. However, to date available data on parasite occurrence before commercial harvesting begins, are scant. This research gathered epizootiological data from weeks 4 to 13 post-transfer, for 153 T. maccoyii sampled from two research and four commercial pontoons. Counts of both parasites in the research pontoons reached levels far heavier than previously documented in ranched T. maccoyii. For sea lice, the prevalence in most pontoons was 100%; the highest intensity reached 495 individuals, and mean counts at the peak of the infection exceeded 265 lice per fish. Almost all of the 5407 individual lice counted were identified as adult C. chiastos (89.44% female, 10.14% male); adult females of two other species were also present, C. amblygenitalis (0.13%), in addition to an undescribed species, C. sp. (0.04%). Lice counts were correlated positively with gross eye pathology scores ( r s,151 df = 0.3394, p = 0.0000), negatively correlated with condition index ( r s,151 df = −0.5396, p = 0.0000), and positively correlated with plasma cortisol ( r s,131 df = 0.3906, p = 0.0000) and glucose ( r s,131 df = 0.2240, p = 0.0096). For the blood fluke, prevalences were less uniform than those of sea lice, with lower rates of infection at the beginning (ranging from 10% to 40%), reaching 100% mid-study, and declining again (40% in one pontoon). The highest intensity reached 441 individual flukes. Fluke counts were negatively correlated with plasma haemoglobin ( r s,151 df = −0.2436, p = 0.0051) and positively with lysozyme ( r s,151 df = 0.3013, p = 0.0019). Fluke counts were also correlated with sea lice counts ( r s,150 df = 0.3143, p = 0.0000). Peaks in these epizootics occurred near the onset of elevated mortalities, which started after 7 weeks of ranching.

Immunohistochemical localization of low density lipoprotein receptor-related protein 1 and α 2-Macroglobulin in retinal and choroidal tissue of proliferative retinopathies

The immunolocalization of the low density lipoprotein receptor-related protein 1 (LRP1) and its ligand α 2-Macroglobulin (α 2M) was examined in tissues from human donor eyes of normal, diabetic and sickle cell disease subjects. Streptavidin alkaline phosphatase immunohistochemistry was performed with a mouse anti-human LRP1 and rabbit anti-human α 2M antibodies. Retinal and choroidal blood vessels were labeled with mouse anti-human CD34 antibody in adjacent tissue sections. Mean scores for immunostaining from the pathological and control eyes were statistically compared. LRP1 immunoreactivity was very weak to negative in the neural retina of normal subjects except in scattered astrocytes. LRP1 expression in diabetic eyes was detected in the internal limiting membrane (ILM), astrocytes, inner photoreceptor matrix, choriocapillaris and choroidal stroma. The ligand α 2M, however, was limited mainly to blood vessel walls, some areas of the inner nuclear layer (INL), photoreceptors, RPE–Bruch’s membrane–choriocapillaris complex, intercapillary septa, and choroidal stroma. In sickle cell eyes, avascular and vascular retina as well as choroidal neovascularization (CNV) were analyzed. In avascular areas, LRP1 immunoreactivity was in innermost retina (presumably ILM, astrocytes, and Muller cells) and INL as well as RPE–Bruch’s membrane–choriocapillaris complex and choroidal stroma. α 2M was very weak in avascular peripheral retina compared to vascularized areas and limited to stroma in choroid. In contrast, in areas with CNV, LRP1 immunoreactivity was significantly decreased in overlying retina and in RPE–Bruch’s membrane and choroidal stroma compared to the controls, while α 2M was elevated in RPE–Bruch’s membrane near CNV compared to normal areas in sickle cell choroid. The mean scores revealed that LRP1 and α 2M in neural retina were significantly elevated in astrocytes and ILM in diabetic eyes ( p ≤ 0.05), whereas in sickle cell eyes scores were elevated in ILM and INL ( p ≤ 0.05). In addition, α 2M immunoreactivity was in photoreceptors in both ischemic retinopathies. In choroid, the patterns of LRP1 and α 2M expression were different and not coincident. This is the first demonstration of the presence of LRP1 and α 2M in human proliferative retinopathies. Elevated LRP1 expression in sickle cell neural retina and diabetic inner retina and choroid suggests that LRP1 plays an important role in ischemic neovascular diseases.

Prevalence of Ocular Fundus Pathology in Patients with Chronic Kidney Disease

The objective of this study was to describe the prevalence of ocular fundus pathology in the Chronic Renal Insufficiency Cohort (CRIC) study, a multicenter, longitudinal study of individuals with varying stages of chronic kidney disease (CKD). In this cross-sectional study, 45 degree digital photos of the disc and macula in both eyes were obtained by nonophthalmologic personnel using a nonmydriatic Canon CR-DGI fundus camera in 1936 individuals who participated in the CRIC study. Photographs were assessed in a masked manner by graders and a retinal specialist at a central photograph reading center. The purpose of this review was to inform participants quickly of conditions that warranted a complete eye examination by an ophthalmologist. Among the 1936 participants who were photographed, 1904 (98%) had assessable photographs in at least one eye. Eye pathologies that required a follow-up examination by an ophthalmologist were identified in 864 (45%) of these 1904 participants. These eye pathologies included, among others, retinopathy (diabetic and/or hypertensive), a finding that was observed in 482 (25%) of these 1904 participants. Three percent (65 participants) of the 1904 participants had serious eye conditions that required urgent follow-up and treatment. Lower estimated GFR and cardiovascular disease were associated with greater eye pathology. Estimated GFR <30 ml/min per 1.73 m(2) was associated with a three times higher risk for retinopathy. We found a high prevalence of fundus pathology in participants with CKD. This finding supports recommendations for regular complete eye examinations in the CKD population.

Triple therapy for neovascular age-related macular degeneration (verteporfin photodynamic therapy, intravitreal dexamethasone, and intravitreal bevacizumab)

Objective: Age-related macular degeneration is a multifactorial disease involving inflammation, neovascularization, and vascular leakage. As a result, a rationale exists for investigating combination treatments that target the different pathological processes involved in this disease. We propose triple therapy consisting of verteporfin photodynamic therapy (PDT), intravitreal bevacizumab, and intravitreal dexamethasone. Design: Retrospective chart review. Participants: Thirty-two eyes of 30 patients were included. None of the patients demonstrated concurrent eye pathology, and none ofthe patients had received previous treatment for their choroidal neovascularization. Methods: One cycle of triple therapy consisted of reduced-fluence PDT (300 mW/cm2 for 83 seconds to deliver 25 J/cm2) followed immediately by an 800 mg (0.08 mL) intravitreal dexamethasone (IVD) injection. At 1 and 7 weeks after PDT and IVD, patients received a 1.25 mg (0.05 mL) bevacizumab injection. At 13 weeks after PDT and IVD, each patient had a repeat optical coherence tomography and fluorescein angiography to assess choroidal neovas-cularization activity. Patients were followed for 12 months. Results: The mean number of treatment cycles was 1.4. The mean number of bevacizumab injections was 2.8. Visual acuity improved from 0.74 (SD 0.33) logMAR (20/100) to 0.53 (SD 0.32) logMAR (20/70) ( p > 0.005). Foveal thickness decreased from 328 (SD 116) mm to 216 (SD 85) μm ( p > 0.001). Ninety-four percent of patients lost fewer than 3 lines, 31% gained more than 3 lines, and 6% lost more than 3 lines. Conclusions: By combining agents with complementary mechanisms of action, triple therapy could maintain visual acuity and macular anatomy while allowing a reduction in the number of anti-vascular endothelial growth factor injections required.

Fluorescence emission and excitation spectra of fluorophores of lipofuscin granules isolated from retinal pigment epithelium of human cadaver eyes

Visible light-induced changes in fluorescence characteristics of lipofuscin granules (LG) isolated from retinal pigment epithelium of human cadaver eyes are compared with the analogous age-related changes and correlated with the content and photooxidation of LG main fluorophore, A2E. We used HPLC to examine changes of LG fluorophore composition with donor age, as well as before and after visible-light irradiation (the latter HPLC tests were also done with synthetic A2E). Visible light induces oxidation of LG fluorophores. As a result, their fluorescence characteristics change: the emission spectrum is blue-shifted by 25–40 nm. The observed age-dependent changes in the relative content of LG fluorophores and their oxidized derivatives were qualitatively similar with those caused by irradiation. To improve the accuracy of a new noninvasive diagnostic method, fundus autofluorescence imaging, it is important to know the ratio of nonoxidized and oxidized fluorophore derivatives depending on age and eye pathology.

Unusual presentation of metastatic carcinoma to the eye.

To describe four patients with an unusual presentation of metastatic carcinoma to the eye, diagnosed by histopathologic and immunohistochemical evaluation of vitrectomy material. Retrospective case series of four patients with metastatic carcinoma to the retina/vitreous. The New York Eye and Ear Infirmary database was searched to identify patients with metastatic carcinoma to the retina or vitreous, diagnosed from 1995 to 2006. Diagnoses were established through histopathologic and immunohistochemical evaluation of vitreous fluid obtained via pars plana vitrectomy. The New York Eye and Ear Infirmary Pathology database search resulted in 19,149 vitrectomy specimens, 4 of which were positive for metastatic carcinoma. The diagnosis was clinically unsuspected in three patients. The oncologic work-up revealed the origin of metastases to be from the breast in two patients and from the lung in two patients. Metastatic carcinoma to the eye can present with clinically innocuous metastases, masquerading as epiretinal membrane and macular hole, central serous chorioretinopathy, rhegmatogenous retinal detachment, retinal granuloma, and endophthalmitis. These findings suggest that submission of vitrectomy specimens for pathologic evaluation should be considered in patients with an oncologic history or in those with atypical clinical presentation.

Giant Choroidal Nevus: Clinical Features and Natural Course in 322 Cases

Evaluation of clinical features and natural course of giant choroidal nevi (diameter >or=10 mm). Retrospective observational case series. We included 322 eyes of 322 patients. Clinic-based study of tumor features, tumor outcome, and vision outcome. Kaplan-Meier analysis was used to assess time to transformation into melanoma. Cox proportional hazards regressions evaluated clinical factors predictive of nevus transformation into melanoma and nevus-related decreased vision (defined as <20/20 and unrelated to other eye pathology). Transformation of giant choroidal nevus into melanoma and nevus-related decreased vision. A medical record review of 4100 patients diagnosed with choroidal nevus identified 322 (8%) giant choroidal nevi. Median nevus basal diameter was 11 mm (range, 10-24). Median thickness was 1.9 mm (range, 0-4.4). Related retinal findings included drusen overlying nevus (n = 261 [81%]), subretinal fluid (n = 26 [8%]), orange pigment (n = 4 [1%]), retinal pigment epithelial (RPE) detachment (n = 6 [2%]), hyperplasia (n = 48 [15%]), fibrous metaplasia (n = 48 [15%]), atrophy (n = 63 [20%]), or trough (n = 6 [2%]). Kaplan-Meier analysis estimated transformation into melanoma in 13% at 5 years and 18% at 10 years. Multivariate analyses revealed factors predictive of transformation into melanoma including involvement or close proximity to the foveola (P = 0.017) and acoustic hollowness (P = 0.052). Nevus-related decreased vision was found in 2.2% of eyes at initial visit and 3.7% at final visit (median 41 and mean 61 months follow-up). Factors associated with nevus-related decreased vision at initial visit included subretinal fluid (P = 0.001), involvement or close proximity to foveola (P = 0.005), RPE detachment (P = 0.033), and nevus-related choroidal neovascular membrane (P = 0.044). Factors predictive of nevus-related decreased vision at final visit included involvement or close proximity to the foveola (P = 0.001) and presence of symptoms at the initial visit (P = 0.032). Giant choroidal nevi can clinically resemble choroidal melanoma but show features of chronicity, such as overlying drusen and RPE alterations. Over time, 18% transformed into melanoma, underscoring the importance of life-long surveillance.

Investigating a possible cause of the myopic shift after combined cataract extraction, intraocular lens implantation, and vitrectomy for treatment of a macular hole

Objective: It has been documented that combination surgery (phacoemulsification, intraocular lens implantation, and vitrectomy) produces a postoperative myopic shift. We hypothesize that the myopic shift seen in patients treated with combination surgery, membrane stripping, and injection of C 3F 8 for treatment of a macular hole is due to an erroneously short preoperative axial length measurement by the IOLMaster. Study Design: Retrospective chart review. Participants: Eleven eyes of 10 patients treated for a stage III or IV macular hole were recruited from a database search of 1 vitreoretinal practice in Regina, Sask. Methods: All eyes included in the study underwent combination surgery, membrane stripping, and injection of C 3F 8. None of the patients demonstrated concurrent eye pathology. Postoperative axial length measurements by the IOLMaster were obtained and compared with the same preoperative measurements. Results: The mean (SD) postoperative myopic shift seen in the study eyes was −0.76 (0.65) D ( z = −2.578, p < 0.01 ).The mean (SD) preoperative and postoperative axial length measurements were 23.54 (1.02) mm and 23.53 (1.01) mm, respectively. No significant difference in axial length was found between the preoperative and postoperative axial length measurements ( t = 0.43, df = 10, p = 0.68). Conclusions: These findings do not support our hypothesis of an erroneous preoperative axial length measurement by the IOLMaster in patients with a stage III or IV macular hole treated with combination surgery, membrane stripping, and injection of C 3F 8. Further studies are required to determine the precise cause of the postoperative myopic shift.

The Role of Oxidative Stress and Inflammation in Dry Eye Disease

Abstract:There is a growing body of evidence to suggest that oxidative stress may be involved in at least the propagation of cellular injury that leads to eye pathology in various conditions including conjunctivochalasis, dry eye disease, age-related macular degeneration, and UV light-induced and to

Histological observationsof the macular epiretinal membranes from pathological myopic eyes with macular hole

：Objective To investigatethe histological changes of the internal limiting membrane (ILM) in pathological myopiceyes, and the relationships between those changes and the formation of macular hole.Methods The clinical data of 34 patients (34 eyes)with pathological myopia and maeularhole, who had undergone vitrectomy were retrospectively analyzed. All the patients had adiopter over--6.00 D, their ocular axial length ranged from 26.00 to 33.12 mm with anaverage of 27.74 mm. There were 5 eyes without retinal detachment (macular holegroup)while the other 29 eyes all had posterior retinal detachment (RD group). A standardthree-port pars plana vitrectomy was performed in all eyes. The existence of Weiss ringwas considered as the sign of posterior vitreous detachment. The epiretinal membranes from34 eyes and ILM specimens from 19 eyes were stained by hematoxylin-eosin (HE) and acetateurany[ acetate-lead citrate, and then investigated under optical microscope andtransmission electron microscope. Results The Weiss ring was observed in 5 eyes during thesurgery, multilayer of vitreous tissue resides on the retinal surface in 24 eyes. Theresults of optical microscope showed that the epiretinal membranes were composed ofvitreous collagen, astrocytes and extracellular matrixes. The results from transmissionelectron microscope showed a sandwich structure (ILM-vitreous collagen-cells) in 5 eyes,and ILM damage, surface traction and astrocytes migration in 1 eye. Conclusions Splittingof posterior surface of vitreous and surface structure change of ILM are the majormechanisms for the formation and progression of macular holes, and even retinal detachmentin high myopic eyes. Key words: Myopia; degenerative/complications; Retinal perforations/etiology; Epiretinal membrane/pathology

Classification of macular retinoschisis in pathological myopic eyes by optical coherence tomography and its clinical applications

Pathological myopic macular retinoschisis can be classified into 4 types based on optical coherence tomography (OCT) images: outer layer retinoschisis, outer + middle layer retinoschisis, outer + inner layer retinoschisis and muhilayer retinoschisis. Currently vitrectomy is the major option to treat this condition as it can remove the posterior vitreous cortex completely and peel the internal limiting membrane (ILM) around the posterior vessels arch. Vitrectomy benefits the visual function significantly for outer layer retinoschisis with foveal detachment, but has no or very little effects on muhilayer retinoschisis. The appropriate starting site for removal of posterior cortex and ILM should be the site without inner layer retinoschisis. The knowledge and understanding of the OCT classification of pathological myopic macular retinoschisis is important for us to chose correct operation methods and determine the prognosis after treatment. Key words: Myopia; degenerative/complications; Myopia; degenerative/surgery; Retinoschisis/diagnosis; Tomography; optical coherence; Editorial

Cataract and Glaucoma Case Detection for Vision 2020 Programs in Africa

To determine if there is a screening test or a combination of screening tests that may be suitable for cataract and glaucoma case detection in Vision 2020 programs in Africa. Design-Screening methods validation study. Setting-Groote Schuur Hospital, Cape Town, South Africa. Subjects-African patients aged 40 years and older with known cataract or with known glaucoma, and accompanying relatives aged 40 years and older with no known eye pathology. Outcome measures-Sensitivity, specificity, positive and negative likelihood ratios, and accuracy of 6 screening tests, used alone and in various combinations. Testing the pinhole visual acuity using a cut point of 6/18 in 1 or both eyes has a sensitivity and specificity greater than 90%, a positive likelihood ratio greater than 10.0, a negative likelihood ratio less than 0.1, and an accuracy greater than 90% for case detection of cataract or glaucoma. Examination of the optic disk with a lens free direct ophthalmoscope using a cut point of 0.7 for the vertical cup:disk ratio combined with testing for an afferent pupil defect has similar values for case detection of glaucoma. These tests may be suitable for use in Vision 2020 programs in Africa.

Ocular rigidity in living human eyes in health and disease

Abstract Purpose It is known that the balance between aqueous humor secretion and outflow rate controls the steady ‐ state average intraocular pressure (IOP). It has been also early identified that blood circulation results to IOP fluctuations practically synchronous to cardiac function. IOP is the primary mechanical load to several ocular structures including the optical nerve head. Methods In‐vivo intraoperative measurement of these quantities as well as secretion/outflow coefficients in humans allowed us to quantify ocular rigidity, IOP and its fluctuations (and pulsatile blood flow) in a series of physiological and pathological eyes. Ocular rigidity, outflow facility and pulsatile ocular blood flow were measured intraoperatively in a cohort of 63 patients undergoing cataract surgery. Measurements were also performed in a series of age related macular degeneration (AMD) patients. Results The eye, is a living structure under a continuously varying mechanical load that is strongly related to ocular haemodynamics. Ocular rigidity ranged from 0.0122 to 0.0343 (mean 0.0208)μl‐1. Outflow facility coefficient (derived from pressure decay curves) was 0.33 (sd 0.15)μl/min/mmHg. Pulsatile ocular blood flow exhibited a strong negative correlation to IOP in all subjects. The ocular rigidity coefficient was higher in wet AMD patients compared to patients with dry AMD and healthy controls. Conclusion There are indications that this mechanical load, associated also to ocular rigidity, can not only inter‐modulate blood flow but also have a long‐term effect on other structures in the eye. Understanding the role of these parameters may contribute to the understanding of ocular disease.

Ocular Manifestations of Long-Term Mascara Use

Mascara, a widely used cosmetic, is associated with eye pathology. The authors report 3 cases of eye problems secondary to long-term mascara use. Two patients had multiple pigmented conjunctival lesions; one of these had a history of melanoma of the hand. Conjunctival biopsy revealed nonmelanocytic pigment granules within conjunctival stroma cells in both cases. The other patient had a history of dry eye, and also showed pigment clumping around a punctal plug. The third patient had canalicular obstruction from a mascara-laden dacryolith ("dacryomascaralith"), the first such case reported. A literature review revealed cases of eyelid dermatitis, infectious keratitis, a conjunctival mass ("mascaroma"), and others. Ophthalmologists should be aware of mascara's associated eye problems. The physical findings combined with a high index of suspicion, especially in cases of heavy mascara use, may allow for an accurate diagnosis and spare the patient an otherwise unnecessary invasive procedure.

Neuroimaging studies in patients with Charles Bonnet Syndrome

Charles Bonnet Syndrome (CBS) is characterized by complex formed and recurrent visual hallucinations in psychologically normal people, and is often associated with eye pathology. Many psychiatrists have taken an interest in CBS because this syndrome could provide clues to the mechanisms underlying visual hallucinations. In the present paper, we review previous neuroimaging studies in patients with CBS and summarize the results of these studies. There could be a fundamental dysfunction in the primary and secondary visual cortices in some patients with CBS, and transient cortical activation occurs in the inferior lateral temporal cortex during the appearance of visual hallucinations in CBS patients. External visual stimuli are perceived in the retina and are transmitted to the primary visual cortex (Brodmann area (BA) 17). The stimuli are transmitted from BA 17 to the secondary visual cortex (BA 18) and then to the visual association cortices (BA 19 and BA 37). In general, our perception of external visual stimuli normally has an inhibitory effect on the endogenous activation of the visual cortex. Visual loss due to certain conditions, of which eye pathology is the most commonly postulated in CBS patients, produces a state of sensory deprivation that releases the visual cortex from regulation by external stimuli, resulting in visual hallucinations (cortical release phenomenon). The results of previous neuroimaging studies suggest that the cortical release phenomenon hypothesis for the occurrence of visual hallucinations in patients with CBS is plausible. In addition, the results indicate that not only eye pathology, but also dysfunction in the primary and secondary visual cortices could result in deprivation of external visual stimuli.

Clinical, legal and ethical implications of the intra-ocular (off-label) use of bevacizumab (avastin)--a South African perspective.

Choroidal neovascularisation is a potentially visually devastating element of various forms of eye pathology. Recent research has focused on neurovascular age-related macular degeneration (AMD) as a cause. AMD can be classified as being exudative (wet) or atrophic (dry). Wet AMD is characterised by a pathological process in which new blood vessels develop in the choroids, causing leakage of fluid and haemorrhage under the retina and leading to localised serous detachment and loss of central vision. Vascular endothelial growth factor (VEGF) stimulates growth of neovascular membranes. Treatments have until recently yielded disappointing results. Ophthalmologists are using intra-ocular injections of bevacizumab (Avastin), an anti-VEGF, to treat AMD. Avastin appears to be safe and effective in the short term, but its intra-ocular administration is entirely off-label. Avastin is registered for treating metastatic colorectal and breast cancer. The off-label use of medication is an important part of mainstream, legitimate medical practice worldwide. Lawyers representing plaintiffs injured by drugs increasingly encounter off-label use claims. From a legal/ethical point of view the off-label use of medication represents a delicate balance between the statutory regulation of medication and a physician's prerogative to prescribe medication that in his or her medical opinion will be beneficial to the patient. The main reason for the controversy created by the off-label use of Avastin is that there are anti-VEGF drugs on the market that have formal approval for the treatment of AMD (and other eye conditions). Lucentis, for example, is extremely expensive, with treatment cost approximately 50 times that of Avastin. Many patients suffering from AMD and macular oedema cannot afford the registered product. The off-label use of Avastin has passed the innovative or experimental stages, as ophthalmologists have used it regularly and openly for a long time, with good success. Such use therefore cannot be considered careless, imprudent or unprofessional. We submit that an ophthalmologist who omits to inform a patient of the availability of Avastin for this form of treatment may be found to be negligent. Protocols developed by the South African Vitreoretinal Society and endorsed by the Ophthalmological Society of South Africa for administering Avastin and other intra-ocular medication intravitreally should be strictly adhered to.

Wolfram syndrome: a clinicopathologic correlation

Wolfram syndrome or DIDMOAD (diabetes insipidus, diabetes mellitus, optic atrophy and deafness) is a neurodegenerative disorder characterized by diabetes mellitus and optic atrophy as well as diabetes insipidus and deafness in many cases. We report the post-mortem neuropathologic findings of a patient with Wolfram syndrome and correlate them with his clinical presentation. In the hypothalamus, neurons in the paraventricular and supraoptic nuclei were markedly decreased and minimal neurohypophyseal tissue remained in the pituitary. The pontine base and inferior olivary nucleus showed gross shrinkage and neuron loss, while the cerebellum was relatively unaffected. The visual system had moderate to marked loss of retinal ganglion neurons, commensurate loss of myelinated axons in the optic nerve, chiasm and tract, and neuron loss in the lateral geniculate nucleus but preservation of the primary visual cortex. The patient's inner ear showed loss of the organ of Corti in the basal turn of the cochleae and mild focal atrophy of the stria vascularis. These findings correlated well with the patient's high-frequency hearing loss. The pathologic findings correlated closely with the patient's clinical symptoms and further support the concept of Wolfram syndrome as a neurodegenerative disorder. Our findings extend prior neuropathologic reports of Wolfram syndrome by providing contributions to our understanding of eye, inner ear and olivopontine pathology in this disease.