Idiopathic ischemic syndromes of the retina and optic nerve and their carotid origin

Most eye problems referred to vascular surgeons for workup of carotid disease are either transient (amaurosis fugax) or partial (retinal branch artery occlusion) visual loss. Patients with more severe total infarcts of the retina (central retinal artery occlusion) or of the head of the optic nerve (“ischemic optic neuropathy”) are seldom suspected of carotid disease and, in the latter case, are generally labeled idiopathic. An explanation for the difference in attitude towards these conditions is suggested. A prescribed carotid etiology for these various ischemic syndromes of the eye and optic nerve was explored in a study of 20 consecutive patients who had acute ischemic eye/optic nerve problems. Special visualization of the neck, orbital, and retinal vasculature was obtained. Sixty percent had ipsilateral and 50% had contralateral carotid artery disease. The ophthalmic artery and the posterior ciliary arteries showed intrinsic lesions each in 25% of cases. Our pilot study concludes that there is strong evidence that most of these ischemic eye syndromes are related to carotid artery disease, which is found in the majority of patients. In a minority of them ischemic problems may be due to arteritis or to intrinsic disease of the ophthalmic artery. A more cohesive approach to the study and treatment of these different entities is supported by the suggestion of a common etiology for most of them. Close collaboration with ophthalmologists will be needed to improve the present management of these eye conditions. (J VASC SURG 1985;2:649-53.)     

The rationale of photocoagulation therapy for proliferative diabetic retinopathy: a review and a model

A model is proposed for initiation and inhibition of growth in retinal vessels including the control of proliferative diabetic retinopathy by photocoagulation. The model assumes that chronic dilatation (constriction) of a retinal blood vessel causes (inhibits) growth. Destruction of rods and cones by photocoagulation allows more choroidal oxygen to reach the inner retina and constrict retinal vessels. The attenuated vessels in late stage retinitis pigmentosa are an analogous and exaggerated effect to that from photocoagulation. The control of proliferative diabetic retinopathy is compared to the cause of retrolental fibroplasma. Following vitrectomy the retina utilizes oxygen from the aqueous which results in dilatation of iris vessels followed by rubeosis iridis. From this model, neovascularization from the disc or angle vessels follows the dilatation resulting from increased flow in their distal vascular beds.     

Retinal abnormalities characteristic of inherited renal disease

Many inherited renal diseases have retinal features that are helpful diagnostically. These include coloboma, drusen, atrophy and pigmentation (retinitis pigmentosa), hamartoma, vascular anomalies, and crystals. Retinal abnormalities occur because the kidney and retina share developmental pathways and structural features including basement membrane collagen IV protomer composition and their vascularity, and because both the kidney and retina are functionally dependent on ciliated cells. Diagnosis of inherited renal disease is important because of the risks of further renal and systemic complications, the implications for other family members, the predictability of the clinical course, and the possibility of treatment. Furthermore, retinal abnormalities may help explain the pathogenesis of the renal disease, and can sometimes be used to monitor its course.     

Transient vision loss

Opinion statement Transient vision loss often presents a diagnostic dilemma and may occur in many different settings. Episodic vision loss is a common complaint and the physician must distinguish whether the transient vision loss is benign or representative of a more serious underlying condition. Common causes of transient vision loss include ischemia and primary ocular pathology. Ischemic causes of vision loss include retinal vascular disease, intermittent optic nerve vascular compromise, or cerebrovascular disease. Many pathologic ocular processes may lead to transient vision loss, including tear film abnormalities and corneal diseases. The authors discuss the clinical presentation and management of transient vision loss, with special attention on characteristics that differentiate vascular disease from primary ocular pathology.     

Retinal vascular occlusion without retrobulbar or optic nerve sheath hemorrhage after retrobulbar injection of lidocaine

We report a case of retinal vascular occlusion in a patient with severe diabetic retinopathy after retrobulbar injection of lidocaine. Several features of the occlusion are of interest: 1) rapid onset and relatively rapid reversal temporally associated with intervention; 2) numerous areas of focal vascular constriction; 3) absence of retrobulbar hemorrhage or dilated optic nerve sheath on CT scan; and 4) recurrence of nonperfusion after a second injection into the inferior peribulbar space. This suggests that patients with severe vascular disease may suffer retinal vascular occlusion after retrobulbar injections in the absence of identifiable retrobulbar or intraoptic nerve sheath hemorrhage. Though the mechanism is uncertain, this unusual complication deserves consideration, since its early recognition could possibly be of benefit in the management of some patients.     

Diagnosis and management of ocular complications of sickle hemoglobinopathies: Part V

Sickle cell retinopathy in its advanced form is complicated by preretinal neovascularization, vitreous hemorrhage, and retinal detachment. Treatment of neovascularization can be performed with photocoagulation. Complications such as retinal breaks, retinal detachments, and choroidally fed neovascularization may result from such treatment. The risks vs. the benefits of various types of photocoagulation are currently being evaluated. Cryotherapy also may be used to treat neovascularization. It is currently being used in eyes with media that are too hazy to permit photocoagulation. It is used commonly during scleral buckling and vitrectomy procedures. In eyes with decreased visual acuity secondary to prolonged vitreous hemorrhage, pars plana vitrectomy can be utilized to produce optically clear media. Complications (including erythrocyte-induced glaucoma), however, may be severe. Retinal detachment can be treated by scleral buckling, but the markedly increased risk of anterior segment ischemia in patients with sickle cell hemoglobin necessitates preoperative, intraoperative, and postoperative prophylactic measures to minimize the risk of this potentially devastating complication. In eyes with retinal detachment with cloudy media and severe vitreous traction, combined scleral buckling and vitrectomy may be necessary. These eyes are extremely fragile, and a successful result is currently obtained in only about 50% of such cases. Hyphemas in patients with sickle cell hemoglobinopathies, whether traumatically or surgically induced, may have devastating effects on the eye. If elevated IOP results decreased vascular perfusion of the eye may cause irreversible damage to the retina and optic nerve. Most antiglaucoma medications, when used in the sickle cell patient, have a narrow margin of safety. Therefore, early surgical intervention for the treatment of sickle cell hyphemas is currently being evaluated.     

Severe hypertensive retinopathy. Increased incidence in renoparenchymal hypertension

In 205 patients with histologically evaluated glomerulonephritis, 69 patients with essential hypertension and 12 patients with renovascular hypertension, the retina was examined and evaluated by fundus photography. Changes of the retina were classified according to the recommendations of WHO: mild to severe changes of retinal arteries were termed as mild hypertensive retinopathy, and exaggerated changes, including exudates, hemorrhages and optic disc changes, as severe hypertensive retinopathy. In spite of the short duration of renal disease and the young age of the patients in many cases, retinal changes in patients with renal hypertension were significantly more severe: especially in focal segmental sclerosis and membranoproliferative glomerulonephritis was severe hypertensive retinopathy observed. Mild hypertensive retinopathy was more prevalent in essential hypertension. When renal disease progresses the retinal findings tended to deteriorate as well. Since the 24-hour blood pressure profile was comparable in most of the groups studied, it was supposed that the vulnerability of the retina and probably other vascular beds (e.g. kidneys) was increased. We conclude that the retina of these patients should be examined even in the case of relatively mild hypertension (greater than 180/100 mm Hg) and early antihypertensive treatment is an important requirement.     

大鼠视神经部分损伤模型的建立

目的 应用动脉瘤夹建立一种新型的大鼠视神经部分损伤模型.方法 使用标定力量为90 g的动脉瘤夹钳夹大鼠眶内段视神经9s建立视神经部分损伤动物模型.采用立体定向上丘荧光金注射逆行标记视网膜神经节细胞(RGCs)的方法,观察损伤2周后RGCs数目的 变化,并对正常及损伤后大鼠视网膜、视神经的形态学进行对比研究.结果 视神经部分损伤后RGCs密度为(778±81)个/mm2,与正常对照组(2047±97)个/mm2、假手术组(2033±117)个/mm2比较差异有统计学意义(P<0.05).形态学研究结果显示,光镜下对照组视网膜各层排列整齐,视神经纵切面纤维排列整齐;钳夹伤组视网膜节细胞层部分胞核呈固缩状,视神经纤维排列紊乱,损伤处可见大量断裂的纤维残端和空泡化的细胞.结论 本方法建立的动物模型具有稳定性好、操作简便的特点,是研究视神经损伤与修复机制较为理想的模型.     

Intraorbital implantation of a stimulating electrode for an optic nerve visual prosthesis. Case report

Research into visual prosthetics is expected to revolutionize the treatment of blind patients with incurable outer retinal degenerative disease. Substantial evidence shows that useful visual sensations can be produced by controlled electrical stimulation of the optic nerve. To make the optic nerve visual prosthesis more acceptable, implantation techniques safer and less invasive than those previously used have been developed. A medial transconjunctival approach is now used to implant a stimulating electrode around the intraorbital section of the optic nerve. This new technique allows sufficient exposure of the nerve after detaching only one rectus muscle and performing a lateral canthotomy. Previously, an electrode was implanted in the intracranial part of the optic nerve, which required more invasive surgery. The new technique was first developed in cadavers and in patients undergoing eye enucleations. Finally, a 68-year-old blind man suffering from retinitis pigmentosa underwent long-term implantation. In this case report the authors describe the technique and outline some of the challenges involved.     

Branch retinal vein occlusion associated with optic nerve drusen: a case report

Proliferative retinopathy secondary to a branch vein occlusion developed in an otherwise healthy 24-year-old women who also had optic nerve drusen. Since the patient sustained a preretinal hemorrhage, quadrantic photocoagulation was applied to the nonperfused quadrant of the retina involved in the occlusion. This case illustrates that compression of a branch retinal vein is another potential complication of optic nerve drusen.     

Topical administration of nepafenac inhibits diabetes-induced retinal microvascular disease and underlying abnormalities of retinal metabolism and physiology

Pharmacologic treatment of diabetic retinopathy via eyedrops could have advantages but has not been successful to date. We explored the effect of topical Nepafenac, an anti-inflammatory drug known to reach the retina when administered via eyedrops, on the development of early stages of diabetic retinopathy and on metabolic and physiologic abnormalities that contribute to the retinal disease. Streptozotocin-induced diabetic rats were assigned to three groups (0.3% Nepafenac eyedrops, vehicle eyedrops, and untreated control) for comparison to age-matched nondiabetic control animals. Eyedrops were administered in both eyes four times per day for 2 and 9 months. At 2 months of diabetes, insulin-deficient diabetic control rats exhibited significant increases in retinal prostaglandin E(2), superoxide, vascular endothelial growth factor (VEGF), nitric oxide (NO), cyclooxygenase-2, and leukostasis within retinal microvessels. All of these abnormalities except NO and VEGF were significantly inhibited by Nepafenac. At 9 months of diabetes, a significant increase in the number of transferase-mediated dUTP nick-end labeling-positive capillary cells, acellular capillaries, and pericyte ghosts were measured in control diabetic rats versus nondiabetic controls, and topical Nepafenac significantly inhibited all of these abnormalities (all P < 0.05). Diabetes-induced activation of caspase-3 and -6 in retina was partially inhibited by Nepafenac (all P < 0.05). Oscillatory potential latency was the only abnormality of retinal function reproducibly detected in these diabetic animals, and Nepafenac significantly inhibited this defect (P < 0.05). Nepafenac did not have a significant effect on diabetes-induced loss of cells in the ganglion cell layer or in corneal protease activity. Topical ocular administration of Nepafenac achieved sufficient drug delivery to the retina and diabetes-induced alterations in retinal vascular metabolism, function, and morphology were inhibited. In contrast, little or no effect was observed on diabetes-induced alterations in retinal ganglion cell survival. Local inhibition of inflammatory pathways in the eye offers a novel therapeutic approach toward inhibiting the development of lesions of diabetic retinopathy.     

外伤性白内障人工晶状体植入术后视觉质量影响性研究

目的探讨对外伤性白内障人工晶状体植入术后视觉质量的影响性研究。方法对42例外伤性外伤性白内障人工晶状体植入术患者进行视觉质量及术后并发症的分析,并通过Logistic回归性分析找出对其视觉质量的影响性研究。结果示伤口大小、初次治疗时间、视网膜脱离、术前有PVR、术前视网膜受损伤、有玻璃体积血、视神经损伤及术后并发症等因素与人工晶体移植的视觉效果有关,P〈0.05。结论人工晶体移植的视觉质量影响因素的研究对预防具有重要的临床作用和价值。     

Ocular problems in the patient with end-stage renal disease

The patient with end-stage renal disease (ESRD) is at risk for development of eye disease. This risk is related to the comorbid conditions that are often seen in ESRD patients as well as to the unique effects of hemodialysis and the uremic state in leading to changes in the conjunctivae, cornea, retina, and macula. The most common ocular complaints in ESRD patients include red, irritated eyes, and may be associated with elevations in the calcium-phosphate product. In those patients with chronically elevated calcium-phosphate products, band keratopathy may result. Other eye conditions include macular edema, ischemic optic neuropathy, elevated intraocular pressure, retinal detachment, and retinal hemorrhage. Prompt recognition of these conditions that may threaten a patient's vision is required. This may prove challenging to the nephrologist in the dialysis unit where a detailed ophthalmological examination is difficult. However, a basic knowledge of the common ocular diseases encountered in the dialysis patient forms a framework for deciding which patients require urgent consultation with an ophthalmologist.     

Minocycline reduces proinflammatory cytokine expression, microglial activation, and caspase-3 activation in a rodent model of diabetic retinopathy

Diabetes leads to vascular leakage, glial dysfunction, and neuronal apoptosis within the retina. The goal of the studies reported here was to determine the role that retinal microglial cells play in diabetic retinopathy and assess whether minocycline can decrease microglial activation and alleviate retinal complications. Immunohistochemical analyses showed that retinal microglia are activated early in diabetes. Furthermore, mRNAs for interleukin-1beta and tumor necrosis factor-alpha, proinflammatory mediators known to be released from microglia, are also increased in the retina early in the course of diabetes. Using an in vitro bioassay, we demonstrated that cytokine-activated microglia release cytotoxins that kill retinal neurons. Furthermore, we showed that neuronal apoptosis is increased in the diabetic retina, as measured by caspase-3 activity. Minocycline represses diabetes-induced inflammatory cytokine production, reduces the release of cytotoxins from activated microglia, and significantly reduces measurable caspase-3 activity within the retina. These results indicate that inhibiting microglial activity may be an important strategy in the treatment of diabetic retinopathy and that drugs such as minocycline hold promise in delaying or preventing the loss of vision associated with this disease.     

The retinal distribution of ganglion cells with crossed and uncrossed projections and the visual field representation in the opossum.

The retinal distribution of ganglion cells with crossed and uncrossed projections in the South American opossum, Didelphis marsupialis, was revealed by delivering HRP to one optic tract or to retinal targets of one hemisphere. The cells with uncrossed projections are restricted to the temporal retina, comprising 1/3 of the total retinal area, with a sharp transition at the naso-temporal boundary. Besides being distributed over the nasal 2/3 of the retina, cells with crossed projections are intermingled with those with uncrossed projections over the entire temporal retina. Quantitative analysis about the representation of the horizontal meridian on four specimens revealed that the maximum density of cells with uncrossed projections is on the average located at 3.2 mm (SD = 0.21), i.e. 34.8 deg, temporal to the optic disk, falling to 10% at 2.1 mm (SD = 0.14) or 22.8 deg. On the other hand, the peak for cells with crossed projections is more nasally placed at 1.8 mm (SD = 0.18), i.e. 19.6 deg. Between these two maxima, the site wherein the densities of cells with crossed and uncrossed projections are about equal is on the average about 2.7 mm (SD = 0.25) form the optic disk, i.e. 29.3 deg. This estimate supports the hypothesis that the retinal intersection of the vertical meridian lies within the region of split representation of crossed and uncrossed ganglion cells. In addition, it was observed that the opossum's retina has a large contingent of cells with uncrossed projections temporal to an eccentricity of 2.7 mm from the optic disk, where it represents roughly 2/3 of the ganglion cells. These data corroborate the relevance of the opossum as a non-primate model for visual work.     

Enhanced recombinant adeno-associated virus-mediated vascular endothelial growth factor expression in the adult mouse retina: a potential model for diabetic retinopathy

Diabetic retinopathy, one of the most serious complications of long-term diabetes, could clinically be divided into two stages: 1) background retinopathy that does not cause visual impairment and 2) proliferative retinopathy, which is a potentially blinding condition. This study aims to investigate the correlation between enhancement of vascular endothelial growth factor (VEGF) expression and neovascular changes. A binary recombinant adeno-associated virus construct producing green fluorescent protein (GFP) and VEGF under the control of the human cytomegalovirus promoter, recombinant adeno-associated virus (rAAV).VEGF.GFP, was produced and injected into the subretinal space of C57BL mice. GFP expression was tracked by fluorescence fundus photography, and VEGF expression was confirmed by immunohistochemistry and enzyme-linked immunoassay. Neovascular changes were monitored by fluorescein angiography and histology and by quantifying the number of inner retinal vessels. GFP expression was found in 100% of injected eyes, and vascular changes were detected in 9 of 10 rAAV.VEGF.GFP-injected eyes. Of these, four demonstrated microaneurysms and five showed moderate to severe leakage. There was a statistically significant increase in blood vessel number in the inner nuclear layer (P < 0.03) and dilatation of retinal veins (P < or = 0.05). This work has demonstrated that the development of different stages of diabetic retinopathy is closely correlated with an increased VEGF level in the retina.     

Optical Coherence Tomography‐Guided Retinal Prosthesis Design: Model of Degenerated Retinal Curvature and Thickness for Patient‐Specific Devices

Retinitis pigmentosa affects over 1.5 million people worldwide and is a leading cause of vision loss and blindness. While retinal prostheses have shown some success in restoring basic levels of vision, only generic, “one‐size‐fits‐all” devices are currently being implanted. In this study, we used optical coherence tomography scans of the degenerated retina from 88 patients with retinitis pigmentosa to generate models of retinal thickness and curvature for the design of customized implants. We found the average retinal thickness at the fovea to be 152.9 ± 61.3 μm, increasing to a maximum retinal thickness of 250.9 ± 57.5 μm at a nasal eccentricity of 5°. These measures could be used to assist the development of custom‐made penetrating electrodes to enhance and optimize epiretinal prostheses. From the retinal thickness measurements, we determined that the optimal length of penetrating electrodes to selectively stimulate retinal ganglion cell bodies and interneuron axons in the ganglion cell layer should be 30–100 μm, and to preferentially stimulate interneurons in the inner nuclear layer, electrodes should be 100–200 μm long. Electrodes greater than 200 μm long had the potential to penetrate through the retina into the choroid, which could cause devastating complications to the eye and should be avoided. The two‐ and three‐dimensional models of retinal thickness developed in this study can be used to design patient‐specific epiretinal implants that will help with safety and to optimize the efficacy of neuronal stimulation, ensuring the best functional performance of the device for patients.     

睫状神经营养因子对不全视神经损伤的保护效应

目的 观察睫状神经营养因子(CNTF)对猫视神经不全损伤后的神经保护效应.方法 制作猫视神经不全损伤模型;CNTF组分别给予CNTF 8μl(1g/L)玻璃体内注射,对照组给予生理盐水8μl;术后15d双侧上丘、外侧膝状体显微注射DiI 5μl逆行神经示踪;术前、术后3、15、30d行视觉诱发电位(P-VEP)检测;术后30 d原位心脏灌注;视网膜铺片,视网膜神经节细胞计数;取术侧视神经组织,光镜和电镜观察视神经形态变化.结果 对照组术侧眼PVEP P-100较CNTF组振幅明显减低,潜伏期明显延长,差异有统计学意义(P<0.01);与手术组相较.CNTF组视网膜神经节细胞存活数[(1256±124)个/mm2]明显高于对照组[(632±61)个/mm2](P<0.01),神经结构更加完整.结论 视神经不全损伤后CNTF玻璃体注射具有视神经保护效应.