Progressive Loss Of Visual Acuity Research Articles

OPA1, encoding a dynamin-related GTPase, is mutated in autosomal dominant optic atrophy linked to chromosome 3q28.

Autosomal dominant optic atrophy (ADOA) is the most prevalent hereditary optic neuropathy resulting in progressive loss of visual acuity, centrocoecal scotoma and bilateral temporal atrophy of the optic nerve with an onset within the first two decades of life. The predominant locus for this disorder (OPA1; MIM 165500) has been mapped to a 1.4-cM interval on chromosome 3q28-q29 flanked by markers D3S3669 and D3S3562 (ref. 3). We established a PAC contig covering the entire OPA1 candidate region of approximately 1 Mb and a sequence skimming approach allowed us to identify a gene encoding a polypeptide of 960 amino acids with homology to dynamin-related GTPases. The gene comprises 28 coding exons and spans more than 40 kb of genomic sequence. Upon sequence analysis, we identified mutations in seven independent families with ADOA. The mutations include missense and nonsense alterations, deletions and insertions, which all segregate with the disease in these families. Because most mutations probably represent null alleles, dominant inheritance of the disease may result from haploinsufficiency of OPA1. OPA1 is widely expressed and is most abundant in the retina. The presence of consensus signal peptide sequences suggests that the product of the gene OPA1 is targeted to mitochondria and may exert its function in mitochondrial biogenesis and stabilization of mitochondrial membrane integrity.

Contractile peripapillary staphyloma

Contractile peripapillary staphyloma is a rare entity with few cases described in the literature. We describe the case of a 75-year-old male who had normal visual acuity and was right eye-dominant during World War II. During the following 35 years, the patient complained of a progressive loss of visual acuity and visual fields in the right eye. He was noted to have a staphyloma with regularly periodic contractile movements in that eye. We discuss the etiology of this entity.

Linkage studies in dominant optic atrophy, Kjer type: possible evidence for heterogeneity.

Dominant optic atrophy, Kjer type, is an autosomal dominant disorder causing progressive loss of visual acuity and colour vision from early childhood. The gene (OPA1) has variable expressivity, a penetrance...

Refinement of the locus for autosomal dominant juvenile optic atrophy to a 2 cM region on 3q28

Juvenile optic atrophy (Kjer type; OPAI) is an autosomal dominant trait with an insidious onset in the first decade of life. The condition is characterized by a progressive loss of visual acuity that usually occurs with severe defects in color vision and visual fields. Genetic linkage analysis of a number of families has already assigned the OPAI locus to the 3q28-qter region, within an estimated region of about 8 cM that is flanked by D3S1601 and D3S1265. Our study of a four-generation English family also supported tight linkage between the OPAI locus and a group of DNA markers from the reported region. Of the 13 markers genotyped in this family, D3S2305 provided the maximum LOD score of 3·91 at θ = 0.00. Inspection of the haplotype transmission in this family identified critical recombinant individuals that refined the location of the OPAI locus to an estimated region of about 2cM that is flanked by two DNA markers of D3S1601 and D3S2748. This refinement should facilitate the molecular cloning of the OPAI gene and the determination of its defective product.

NATURAL HISTORY OF SUBFOVEAL SUBRETINAL HEMORRHAGE IN AGERELATED MACULAR DEGENERATION

The authors describe the natural history of subfoveal subretinal hemorrhage (for which laser treatment was not indicated) in age-related macular degeneration. A retrospective review of data was performed at a tertiary retinal referral center for 41 eyes from 40 patients with age-related macular degeneration examined during an 18-month period. All patients had at least 3 months of follow-up, as well as subfoveal subretinal hemorrhage that made up more than 50% of a neovascular lesion-as documented by fluorescein angiography-and therefore, did not meet criteria for laser treatment. The number of lines of visual acuity lost or gained in each eye during follow-up was calculated; presenting characteristics were evaluated as predictors of visual outcome. A progressive loss of visual acuity from baseline was observed throughout the 3-year follow-up period in most eyes. At 36 months, a mean of 3.5 lines of visual acuity had been lost in the 16 eyes examined; 44% of eyes had lost 6 or more lines of visual acuity. The percentage of patients who sustained a spontaneous improvement of 3 or more lines of visual acuity decreased from 31% at 12 months to 21% at 36 months of follow-up. Univariate linear regression analysis demonstrated significant relationships of initial size of the hemorrhage, elevation of the retina by the hemorrhage, and size of the entire lesion with visual outcome at the 12-month and 36-month examinations (P < 0.05). Although this study confirms that some eyes with subfoveal subretinal hemorrhage associated with age-related macular degeneration have poor prognoses, the visual acuity of other eyes did not deteriorate. These findings underscore the importance of evaluating the role of therapeutic interventions such as surgery to remove subretinal hemorrhage in randomized clinical trials.

Original papers: Ocular motility disorders after surgery for retinitis pigmentosa ‘Cuba-therapy’

Since 1988 Cuban ophthalmologists use a combined 'therapy' for retinitis pigmentosa. The treatment, comprising ozonization, electrostimulation, vasodilators, and an unknown surgical procedure after O. Pelaez, is said to stop the progression of the disease. While the nature of the operation remains unclear and scientific proof of its efficacy is still absent, reports about persisting active and passive impairments of ocular motility are becoming more frequent. The authors present the pre-, intra- and postoperative findings in two patients who developed persisting diplopia after Pelaez's operation. In both cases, one with +14° esotropia, the other with up to 25° incyclotropia and bilateral Brown's syndrome, binocular single vision was restored by recession of the medial rectus and superior oblique muscles. Comparing the functional findings before and one year after 'Cuba-therapy', the treatment fails to prevent progressive loss of visual acuity and visual field. Therefore, the Cuban treatment trial should not be recommended in retinitis pigmentosa.

Optic nerve decompression surgery improves visual function in patients with pseudotumor cerebri.

Papilledema from pseudotumor cerebri can cause severe loss of visual acuity and visual field. We performed optic nerve decompression surgery on 17 patients with pseudotumor cerebri who, despite maximum conventional therapy, developed progressive loss of visual acuity and/or visual field. Postoperatively, visual acuity improved or stabilized in 33 of 34 eyes (97%). Visual fields improved in 20 of 21 eyes that underwent surgery. Optic nerve decompression surgery relieves local cerebrospinal fluid pressure on the optic nerve. Progressive loss of visual function associated with pseudotumor cerebri can be reversed or stabilized with optic nerve sheath decompression surgery.

Optic Nerve Decompression Surgery Improves Visual Function in Patients with Pseudotumor Cerebri

Papilledema from pseudotumor cerebri can cause severe loss of visual acuity and visual field. We performed optic nerve decompression surgery on 17 patients with pseudotumor cerebri who, despite maximum conventional therapy, developed progressive loss of visual acuity and/or visual field. Postoperatively, visual acuity improved or stabilized in 33 of 34 eyes (97%). Visual fields improved in 20 of 21 eyes that underwent surgery. Optic nerve decompression surgery relieves local cerebrospinal fluid pressure on the optic nerve. Progressive loss of visual function associated with pseudotumor cerebri can be reversed or stabilized with optic nerve sheath decompression surgery.

Surgical Removal of Subfoveal Neovascularization in the Presumed Ocular Histoplasmosis Syndrome

We treated two patients with presumed ocular histoplasmosis, subfoveal neovascular membranes, and progressive visual acuity loss to 20/400. Vitreoretinal surgical techniques were used to remove the subfoveal membranes. Visual acuity returned to 20/20 with seven months of follow-up in one patient (Case 1) and to 20/40 with three months of follow-up in the other patient (Case 2). No evidence of persistent or current subretinal neovascular membranes in either patient have been noted. These preliminary results suggest that vitreoretinal surgical techniques may be successful in mechanically removing subfoveal neovascular membranes with preservation of overlying neurosensory retina and thus preservation of central visual acuity.

OPTIC NERVE SHEATH DECOMPRESSION FOR PSEUDOTUMOR CEREBRI

• We studied optic nerve sheath decompressions for pseudotumor cerebri performed at the Kresge Eye Institute, Detroit, over the past year. Six patients (ten eyes) were operated on. Visual function improved in all ten eyes. A decision to operate was based on progressive loss of visual acuity or visual field unresponsive to medical therapy, accompanied by echographic evidence of a distended optic nerve sheath (positive 30° test). Follow-up ranged from four to 11 months. Four patients underwent subarachnoid iopamidol (Isovue) contrast injection followed by orbital computed tomography. The subarachnoid space totally filled in all patients. No evidence of fibrosis or obstruction of the optic nerve sheath existed; however, leakage of dye from the optic nerve sheath could not be demonstrated. Postoperative complications included transient diplopia and transient atonic pupil (one patient each). Our results indicate that optic nerve sheath decompression improves and protects visual function in patients with pseudotumor cerebri who demonstrate progressive visual field loss and fluid in the optic nerve sheath.

Complete External Ophthalmoplegia in a Case of Pseudotumor Cerebri

SYNOPSISA 28 year old woman was admitted to the hospital with a 4 month history of headaches and blurred vision and a 2 week progressive loss of visual acuity. On examination she was found to have complete external ophthalmoplegia, florid papilledema and an otherwise normal neurologic examination. Cerebrospinal fluid pressure and protein supported the diagnosis of pseudotumor cerebri. A normal cerebral angiogram and “slit‐like” ventricles on brain computed tomography supported the diagnosis. She was treated with cortico‐steroids, and acetazolamide and underwent optic nerve fenestration bilaterally. This resulted in complete resolution of the ophthalmoplegia and papilledema.

Limitation and Over-utilization of Angiographic Services

Fluorescein angiography has increased our understanding of the pathophysiology and appearance of most fundus disorders. Increased experience with the stereoscopic slit-lamp examination of the fundus has made it easier to predict what subsequent angiograms will demonstrate, and fluorescein studies are currently usually not required to make an appropriate diagnosis. Most cases of age-related macular degeneration and diabetic retinopathy can be managed without angiography, since most of the former are associated only with drusen and modest and progressive visual acuity loss and most cases of diabetic retinopathy are not associated with loss of visual acuity or with proliferative lesions. Angiography is an invaluable tool in evaluating newly symptomatic patients with the possibility of choroidal neovascularization, and it is also of great value in evaluating causes of visual acuity loss in diabetics as well as in the documentation of nonperfusion of their peripheral retinas.

Unilateral Papilledema in 'Benign' Intracranial Hypertension (Pseudotumor Cerebri)

Three patients with benign intracranial hypertension ([BIH], or pseudotumor cerebri) had verified increased CSF pressure and unilateral papilledema. One patient had slowly progressive loss of visual acuity until unilateral optic nerve sheathotomy was performed. One patient had spontaneous venous pulsation in the unaffected eye. The diagnosis of BIH must be considered even in the absence of bilateral papilledema.

Clinical and Computed Tomographic Findings in the Foster Kennedy Syndrome

A 52-year-old man had progressive loss of visual acuity in his left eye associated with anosmia of five years duration. Clinical findings included papilledema in the right eye and optic atrophy in the left eye. A diagnosis of Foster Kennedy syndrome was made. Careful attention to the ophthalmoscopic appearance of the left eye disclosed optic disk swelling in regions without significant atrophy as well as dilated retinal veins. Both of these signs suggested increased intracranial pressure, rather than a primary anterior ischemic optic neuropathy. High resolution computed tomographic scanning confirmed the presence of a large subfrontal meningioma and an expanded right optic nerve sheath, consistent with the papilledema noted clinically.

Orbital dysplasia in neurofibromatosis.

A dysplasia of the bony walls of the orbit is one of the congenital anomalies associated with generalized neurofibromatosis (1–6). Orbital dysplasia may be mistaken clinically and radiographically for neoplasm or chronic subdural hematoma within the middle cranial fossa unless its characteristic plain film and angiographic findings are appreciated. Plain Skull Film Findings The plain skull film findings of 7 patients with neurofibromatosis and orbital dysplasia, ranging in age from eighteen months to fifty-seven years, are summarized in Table I. All 7 showed obvious stigmata of neurofibromatosis, e.g., café au lait spots, subcutaneous tumors, or skeletal anomalies. The major presenting complaint in all cases was pulsating exophthalmos. Radiographs of the skull in all 7 patients demonstrated a dysplastic sphenoid bone complex. This consists of hypoplasia of the greater and lesser sphenoid wings, resulting in (a) elevation of the lesser sphenoid wing, (b) widening of the superior orbital fissure, and (c) lateral displacement of the oblique orbital line. In addition, there is ipsilateral downward tilting of the floor of the sella turcica and enlargement of the boundaries of the middle cranial fossa in all directions. The ipsilateral orbit is also enlarged, with resultant hypoplasia of the adjacent ethmoid and maxillary sinuses (Fig. 1). Radiographic studies of the optic foramina were obtained in 5 of the 7 cases. In 2 the optic canal on the side of the orbital dysplasia was absent, and in a third the bony strut forming the lateral wall of the canal was very thin and the foramen was enlarged. The remaining 2 patients had intact canals which were enlarged on the side of the orbital dysplasia. One of these patients suffered progressive loss of visual acuity, a symptom not encountered in the other cases. Craniotomy disclosed an infiltrating glioma of the optic nerve and chiasm as well as orbital dysplasia. Surgical repair of the posterior orbital area was carried out in 3 additional patients. In none of these was tumor encountered within the middle cranial fossa. In all 4 surgically confirmed cases, the anterior portion of the temporal lobe had herniated through the defect in the posterior orbital wall, displacing the globe forward and producing the clinically evident exophthalmos. Of the 3 remaining cases not surgically confirmed, 2 patients have lived with their disease for forty-seven and fifty-three years respectively; the third, a young adult, had been followed for twelve years without evidence of tumor mass within the middle cranial fossa. Angiographic Findings Carotid angiography was performed in 4 of the 7 patients (Figs. 2 and 3). In each case, the angiogram was requested to exclude a concomitant middle cranial fossa tumor; however, no tumor was demonstrated in any patient. The characteristic angiographic changes observed on these 4 patients are listed in Table II.