Retinal Sequelae Research Articles

Opticopathies in the differential diagnosis of retinal diseases - part 2

Due to the close anatomical, functional and trophic relationships between the optic nerve and retina, a wide variety of diseases affecting both structures have reciprocal effects on each other, which must be considered in the differential diagnosis to avoid misdiagnosis. Therefore, it is essential to assess pathological changes in both structures in context to differentiate the type and location of the primary lesion from its consequences, as well as to correctly classify coincidences and disease-specific lesion patterns in both organ components.This article highlights the typical symptom constellations and lesion patterns of optic neuropathies and retinopathies. An attempt is made to identify the reciprocal characteristic relationships of the respective lesions in both structures in various disease groups, as well as to present their respective roles in the differential diagnosis.In this second part, acquired optic neuropathies in the context of vascular and systemic diseases and possible accompanying retinal findings, as well as symptom constellations and courses, are differentiated, discussing arteritic and non-arteritic (anterior) optic neuropathies, their causes and differential diagnosis. The combined involvement of the optic nerve and retina in the context of posterior infectious and non-infectious uveitis is also shown. Finally, various dysgenetic optic neuropathies, their differentiation and possible retinal sequelae are presented.It is demonstrated and exemplified how important it is in general, but also specifically in regard to the disease groups discussed in this article, to have a careful and targeted diagnostic approach in each case, considering both the retinal and optic nerve findings, in order to avoid misdiagnosis.

Central macular morphology and optic nerve fibre layer thickness in young adults born premature and screened for retinopathy of prematurity.

To investigate central retinal morphology and optic retinal nerve fibre layer (RNFL) in prematurely born young adults and compare to term born controls. The participants were 59 prematurely born individuals, with a birthweight ≤1.500 g, and 44 term born controls, all 25-29 years of age. Visual acuity (VA) and contrast sensitivity (CS) were assessed. The retinal macular thickness, ganglion cell-inner plexiform layer (GC-IPL) thickness and RNFL thickness were assessed with Cirrus optical coherence tomography (OCT). Central macular thickness was increased (mean 26.7 μm) in prematurely born individuals compared to controls. The macular GC-IPL was thinner (mean 3.84 μm), also when excluding those with previous retinopathy of prematurity (ROP) and those with neurological complications. Gestational age at birth and previous treatment of ROP were risk factors for a thicker macula, however, not for reduced GC-IPL. The average peripapillary RNFL was thinner (mean 4.61 μm) in the prematurely born individuals, also when excluding those with previous ROP and/or neurological complications. Within the prematurely born group, treated ROP was correlated with increased average RNFL. Further, both better VA and CS were associated with thinner optic nerve RNFL and thicker average GC-IPL. Macular and optic nerve morphology were influenced by premature birth as assessed with OCT in adult individuals. Gestational age at birth and treatment for ROP seemed to affect central macular thickness, and treated ROP affected the peripapillary RNFL. Thus, retinal sequelae remained in adulthood.

Failure of preventive measures leading to mother-to-child hiv transmission. Case report.

Despite significant advances in antiretroviral treatment (ARV) and HIV infection prevention, about 400 children worldwide are still diagnosed daily with HIV infection, most cases due to perinatal transmission. It is estimated that the knowledge and rigorous application of prophylactic measures to reduce the vertical transmission of infection would significantly reduce this risk to less than 1%. We report the case of a 5 months old infant coming from a pregnancy with HIV risk and multiple risk factors for transmission of the vertical infection, who did not receive postnatal testing and treatment. The diagnosis was established during infancy, falling into the AIDS stage by cytomegalovirus (CMV) disease with retinal sequelae occlusion. ARV treatment was initiated late, but from the moment of diagnosis, requiring further changes due to drug interactions, lack of availability and resistance to TARV. Although the patient’s progression was marked by severe comorbidities: sequelae of CMV disease, mixed HIV and CMV encephalopathy, pulmonary tuberculosis, repetitive respiratory and digestive opportunistic infections, the evolution of immunological parameters was slowly favorable under treatment. Proper implementation of prophylactic measures in the newborn and the pregnant woman could have significantly reduced the risk of HIV transmission to the patient, with a high probability that she would not have been infected. The case reported reflects the failure of strategies to prevent HIV / AIDS infection in pregnant women and newborns; conclusions must be drawn to avoid similar situations.

Retinal Sequelae in Adults Treated With Cryotherapy for Retinopathy of Prematurity.

Cryotherapy, introduced in the mid-1980s, was the first treatment of severe retinopathy of prematurity (ROP) and resulted in ablation of larger retinal areas than did its later substitute, laser treatment. We defined the characteristics of the retinal structure and assessed visual function, in adult ex-preterms treated with cryotherapy. A total of 28 ex-preterms, included in a prospective study of infants born in Stockholm between September 1988 and March 1993, were treated with cryotherapy because of severe ROP. Of these individuals, 14 took part in this follow-up study and underwent ophthalmologic assessment including visual acuity, fundus photography, perimetry, and retinal imaging using optical coherence tomography (OCT) in their third decade of life. Their gestational ages were 24 to 28 (median 25) weeks at birth. The ex-preterms had reduced foveal depth (P < 0.0001) and increased thickness of the temporal retinal nerve fiber layer (RNFL; P > 0.001). A thicker temporal RNFL was not correlated with a thicker ganglion cell layer (P = 0.41, r = 0.29) as in controls (P = 0.0015, r = 0.78). Extreme thickening was seen in patients with pronounced retinal dragging. In their third decade of life, ex-preterm adults treated with cryotherapy for ROP have major microstructural retinal abnormalities in terms of reduced foveal depth and an altered distribution of the peripapillary RNFL. The main contributors seem to be gestational age and ROP rather than the cryotherapy. The possibility to evaluate the retinal structure in these individuals, with today's conventional OCT, is limited by those anatomic deviations.

No retinal apoptosis in mouse model of Opa1 dominant optic atrophy despite visual loss

Abstract Purpose Autosomal dominant optic atrophy (ADOA) due to mutations in OPA1 is a slowly progressive optic neuropathy. OPA1 is ubiquitously expressed and plays a key role in mitochondrial fusion. Heterozygous Opa1 mutant mice (B6;C3‐Opa1Q285STOP), with previously reported visual defects and optic nerve changes on EM, were assessed for evidence of cellular effects and retinal sequelae. Methods The level and processing of Opa1 were studied by Western blot. Membrane potential was assessed by JC‐1 in isolated mitochondria. Mitochondrial morphology was investigated using Mitotracker staining on E13.5 mouse embryonic fibroblasts (MEFS). End‐organ evidence for apoptosis was explored on TUNEL stained retinal sections. Results The heterozygous mutation leads to ca. 50% reduction in Opa1 protein in mitochondria. Despite this there is no statistically significant reduction in the average mitochondrial membrane potential in the retina and brain by 5 months of age. Although Opa1 +/‐ MEFS demonstrate a 15% increase in the number of cells showing mitochondrial fragmentation their growth and survival characteristics after oxidative stress were not significantly affected. There was no increased apoptosis in retinal sections from mutant animals. Conclusion A 50% reduction in Opa1 protein, capable of causing a defect in mitochondrial morphology in MEFS, in the presence of visual dysfunction and morphological changes on electron microscopy in the optic nerve, nevertheless does not appear to lead to a significant increase in apoptosis in retina. This suggests that dysfunction of RGCs rather than overt loss may be important in the pathophysiology of the disease.

Specific deficits in visual electrophysiology without retinal cellular apoptosis in a mouse model of dominant optic atrophy

Abstract Purpose Autosomal dominant optic atrophy (ADOA) due to mutations in OPA1 is a slowly progressive optic neuropathy. OPA1 is ubiquitously expressed and plays a key role in mitochondrial fusion. Heterozygous Opa1 mutant mice (B6;C3‐Opa1Q285STOP), with previously reported visual defects and optic nerve changes, were assessed for retinal sequelae. Methods ERGs and VEPs were recorded in 12 month old B6;C3‐Opa1Q285STOP mice (n=4) and age/sex matched wildtype littermate controls. Full scotopic and photopic intensity series were recorded in response to brief (4 ms) single flash stimuli delivered in a ganzfeld dome. End‐organ evidence for apoptosis was explored on TUNEL stained retinal sections. Results Quantification of the major ERG components (a‐wave and b‐wave) confirmed no detectable difference in the amplitude or implicit time of scotopic ERGs across the full intensity range tested. This was also true for the VEP components. Quantification of the photopic ERG responses revealed a significant reduction in the PhNR amplitude in Opa1+/‐ animals relative to wildtypes at the brightest intensity tested. The photopic VEP was also abnormal in mutant mice. There was no increased apoptosis in retinal sections from mutant animals. Conclusion Opa1+/‐ mice display a functional deficit on electrophysiology that is indicative of specific ganglion cell dysfunction. Despite a 50% reduction in Opa1 protein there does not appear to be a significant increase in apoptosis in the retina. This suggests that the protein truncating mutation in this model may lead to RGC dysfunction without triggering RGC death.

Triamcinolone-Associated Crystalline Maculopathy

To describe the findings of a new crystalline maculopathy exclusively affecting individuals who have previously received intravitreous triamcinolone acetonide injections. In a retrospective, observational, noncomparative case series, 21 eyes of 13 patients referred over a 9-year period were identified as having a characteristic crystalline maculopathy. Each patient underwent detailed historical questioning and comprehensive ocular evaluation, including formal retinal examination, fundus photography, fluorescein angiography, and optical coherence tomography. Each of the 21 eyes was treated with intravitreous triamcinolone (preserved in all but 2 eyes) for macular edema (18 eyes due to diabetes, 2 due to pseudophakic cystoid macular edema, and 1 due to a vein occlusion). The crystals were superficial, refractile, white or yellow-green, asymmetric in distribution, and deposited as a cluster in the central macula or in a perifoveal distribution. The crystals were benign and unassociated with visual deficit. Preretinal hyperreflective deposits were noted with optical coherence tomography. Two eyes underwent vitrectomy with membrane peeling, and the crystals were no longer present postoperatively. We describe a novel syndrome of crystalline maculopathy associated with a history of intravitreous triamcinolone injections. The crystals are refractile, multicolored, located in the posterior pole, and unassociated with obvious visual deficit or retinal sequelae. The predominantly white color and superficial location of the crystals indicate that they may result from aggregation and clumping of insoluble components of triamcinolone.

518 Retinal sequelae of severe pregnancy induced hypertension

518 Retinal sequelae of severe pregnancy induced hypertension

An Experimental Model of Carotid Artery Occlusive Disease

To develop an animal model for acute carotid artery occlusion suitable for studying the retinal sequelae of this disease, we performed bilateral and unilateral common carotid artery ligations on mature pigmented rats. Bilateral ligation consistently resulted in a characteristic pathologic retinal appearance, paralleling the retinopathy of carotid artery occlusive disease in humans, demonstrated by fundus photography and fluorescein angiography. Any abnormalities found in the rats with unilateral ligations were inconsistent and less severe, although fluorescein angiography proved to be more sensitive than ophthalmoscopy for detecting these subtle changes. Pepsin-trypsin retinal digests disclosed extensive disruption of the microvasculature in the eyes of bilaterally ligated animals. This model should prove to be useful in examining the reversibility of the ocular findings as well as evaluating central nervous system abnormalities after carotid artery occlusion.

Presumed Ocular Histoplasmosis Syndrome

The fundus photographs of 308 patients with presumed ocular histoplasmosis syndrome (POHS) were examined. Bilateral macular involvement was found in 20% of the cases. The incidence of maculopathy, peripapillary lesions, and peripheral "punched-out" lesions in one fundus and only peeipapillary changes in the fellow eye was 12%. The incidence of these features in one fundus and clinically inactive, atrophic scars in the posterior pole of the fellow eye was 23%. Twenty-five patients with atrophic lesions in the macular area of the fellow eye were followed for an average of 24 months. Six patients (24%) demonstrated activation of eight previously documented atrophic lesions resulting in macular involvement. One patient also demonstrated activation from a pre-existing juxtapapillary lesion. None of the remaining 18 patients exhibited any evidence of serous or hemorrhagic retinal sequelae in the fellow eye.