Analyses of shape of eyes and structure of optic nerves in eyes with tilted disc syndrome by swept-source optical coherence tomography and three-dimensional magnetic resonance imaging.

PURPOSE: To evaluate the deeper structures of the optic nerve and to analyze the shape of eyes with tilted disc syndrome (TDS) by swept-source optical coherence tomography (OCT) and three-dimensional magnetic resonance imaging (3D MRI). METHODS: The medical records of 54 eyes of 36 patients with TDS were reviewed. The patients with TDS and high myopia were analyzed separately from those without high myopia. All the eyes were examined with a swept-source OCT, and 22 of the eyes were examined by 3D MRI. RESULTS: A total of 38 eyes of 29 patients were highly myopic and 16 eyes of 15 patients were not highly myopic. The representative OCT findings of the optic disc were: a sloping of the lamina cribrosa posteriorly from the upper part to the lower part, a protrusion of the upper edge of Bruch's membrane, and choroid. The distance and the depth of the most protruded point from the fovea were significantly greater in the eyes with non-highly myopic TDS than those with highly myopic TDS. In the 3D MRI, the lower part of the posterior segment was protruded outward, and the optic nerves attached at the upper nasal edge of the protrusion. CONCLUSIONS: The abnormalities detected by swept-source OCT and 3D MRI analyses indicate the possibility that the essential pathology of TDS is a deformity of the inferior globe below the optic nerve, and the positional relation between the fovea and the inferior protrusion determines the degree of myopia.

Characteristics of intrachoroidal cavitation located temporal to optic disc in highly myopic eyes.

PURPOSE: To investigate the anatomic characteristics of eyes with pathological myopia and peripapillary intrachoroidal cavitation (ICC) located temporal to the optic disc. METHODS: A total of 125 with pathologic myopia were scanned with swept-source optical coherence tomography (OCT). Temporal ICC was defined as ICC located temporal to the optic disc seen in horizontal OCT section through the optic disc center. Definition of pathologic myopia was refractive error >8.00 diopters (D) or an axial length >26.5 mm. RESULTS: In all, 17 eyes of 16 patients had temporal ICC. All of the eyes had temporal or temporally wider annular conus. The ICC was observed temporal to the optic disc in 15 of 17 eyes, and 2 of the remaining eyes also had inferior ICC. Even in the two eyes with both temporal and inferior ICC, the temporal ICC was much wider than the inferior ICC. Inner retinal defect at the border of conus and temporal ICC was detected in two eyes. The temporal ICC was extensive in the posterior fundus with the average width of 1467.8 ± 1328.1 µm (range; 442-6200 µm) in a horizontal section. In two eyes, the temporal ICC extended beyond the central fovea. CONCLUSIONS: Peripapillary ICC can develop temporal to the optic disc without involving the area inferior to optic disc in highly myopic eyes. Temporal ICC appeared much wider than inferior ICC, which is usually restricted to the area around the optic disc. The possible reasons why ICC develops in temporal to the optic disc are presented.

ARMS2/HTRA1 and CFH polymorphisms are not associated with choroidal neovascularization in highly myopic eyes of the elderly Japanese population.

PURPOSE: The purpose of this study was to investigate whether the genetic risk factors of age-related macular degeneration (AMD) are associated with the development of choroidal neovascularization (CNV) in highly myopic eyes of elderly Japanese. METHODS: Highly myopic elderly Japanese patients with and without CNV were genotyped for three AMD-associated single nucleotide polymorphisms (SNPs), namely rs10490924 (A69S) of ARMS2, rs11200638 of HTRA1, and rs1061170 (Y402H) of complement factor H (CFH), with the TaqMan SNP assay. One hundred and eighty-three unrelated highly myopic (axial lengths>26.00 mm or refractive errors>-6.0 diopters) Japanese patients with CNV who were >or=50 years of age (mean age+/-standard deviation of 62.7+/-6.3 years) and 170 highly myopic patients without CNV who were >or=50 years old (62.3+/-7.1 years) were studied. The differences in the genotypic distributions for the three SNPs between the two groups were tested with the Trend chi2 test, and logistic regression analyses were performed for age and gender adjustment. RESULTS: No significant difference was detected in the distribution of the three SNPs, rs10490924 (P>0.1), rs11200638 (P>0.1), and rs1061170 (P>0.5), between the two groups even after adjustments for age and gender differences. CONCLUSION: The genetic risk factors of AMD related to these SNPs do not contribute significantly to the development of CNV in a highly myopic elderly Japanese population.

Progression from macular retinoschisis to retinal detachment in highly myopic eyes is associated with outer lamellar hole formation.

AIMS: To investigate the morphological changes that occur during the development of an early retinal detachment (RD) from a myopic macular retinoschisis (MRS) by optical coherence tomography (OCT). METHODS: The OCT images of five eyes of five consecutive patients with myopic MRS who developed an RD during the follow-up period were studied. RESULTS: The progression from MRS to early RDs went through four stages. In stage 1, OCT images appeared to show a focal irregularity of the thickness of external retina. In stage 2, an outer lamellar hole developed within the thickened area and a small RD developed. In stage 3, the column-like structures overlying the hole seemed to be separated horizontally, and the outer lamellar hole appeared to be larger vertically. In stage 4, the upper edge of the external retina was further elevated and attached to the upper part of the retinoschisis layer accompanied by further enlargement of the RD. CONCLUSIONS: This longitudinal study showed that the progression from myopic MRS to RD passes through four stages, and the formation of an outer lamellar hole predisposes the retina to a RD. These OCT findings might be useful for considering the surgical indication for eyes with a myopic MRS.

Peripapillary crescent enlargement in highly myopic eyes evaluated by fluorescein and indocyanine green angiography.

AIMS: To evaluate angiographic features of myopic crescents using fluorescein angiography (FA) and indocyanine green angiography (IA). METHODS: FA and IA angiograms of 88 highly myopic eyes (47 consecutive patients) were reviewed. The follow up period ranged from 5-28 years. RESULTS: FA revealed two zones of the myopic crescent: a consistently hypofluorescent inner zone and an outer zone with delayed choroidal filling. IA revealed dislocation of the Zinn-Haller ring to the border between the two zones. Myopic crescent enlargement occurred in 68.1%. Only the outer zone increased significantly in most of the eyes with enlarged crescents. CONCLUSIONS: The inner zone might develop as a result of mechanical stretching, and the outer zone might be the result a secondary circulatory disturbance and mechanical stretching.

Patchy atrophy and lacquer cracks predispose to the development of choroidal neovascularisation in pathological myopia.

AIMS: To determine the incidence and predisposing findings for choroidal neovascularisation (CNV) in a large series of highly myopic patients. METHODS: The medical records of 218 consecutive patients (325 eyes) with myopic fundus changes in the macula were reviewed. The incidence of CNV during a follow up of at least 3 years of highly myopic patients and identification of predisposing findings for the development of myopic CNV were examined. RESULTS: Among 325 highly myopic eyes examined, 33 eyes (10.2%) developed myopic CNV. The incidence was higher (34.8%) among the fellow eyes of patients with pre-existing CNV than among eyes of patients without pre-existing CNV (6.1%). CNV developed in 3.7% with diffuse chorioretinal atrophy, in 20.0% with patchy atrophy, and in 29.4% with lacquer cracks. CONCLUSION: Approximately one in 10 highly myopic eyes developed myopic CNV in average 130.2 months. Patchy atrophy and lacquer cracks were shown to be important predisposing findings for CNV development.

Novel mechanism for age-related macular degeneration: an equilibrium shift between the angiogenesis factors VEGF and PEDF.

We investigated gene expression profiles of vascular endothelial growth factor (VEGF) and pigment epithelium-derived factor (PEDF) in differentiated and non-differentiated retinal pigment epithelial (RPE) cells during oxidative stress. Human RPE cells were grown in culture on laminin-coated flasks to obtain differentiated features. Cells cultured on plastic were used as non-differentiated controls. After confluence, hydrogen peroxide (H2O2) was added for 48 h, then, total RNA was extracted and used for RT-PCR and Northern blot analysis. Medium conditioned by RPE was used for ELISA, Western blotting, and in vitro angiogenesis assay. As a result, differentiated RPE cells expressed significantly higher levels of VEGF protein, as compared to their non-differentiated counterparts. The expression pattern remained consistent even after cellular exposure to H2O2. Conversely, while elevated levels of PEDF transcript and protein were seen in differentiated RPE cells, compared to non-differentiated cells, a marked decrease at both PEDF mRNA and protein levels was seen after treatment with H2O2. Moreover, this decrease in PEDF expression was dosage dependent. In in vitro angiogenesis assay, conditioned medium from differentiated human RPE cells after exposure to H2O2 showed a dramatic increase in tubular formation and migratory activity of microvascular endothelial cells. These data suggest that, in physiological conditions, a critical balance between PEDF and VEGF exists, and PEDF may counteract the angiogenic potential of VEGF. Under oxidative stress, PEDF decreases disrupting this balance. This equilibrium shift may be significant in promoting a pathological condition of RPE cells and contributing to choroidal neovascularization in age-related macular degeneration.

The quality of life in patients with pathologic myopia.

PURPOSE: To evaluate the functional status in daily life and the quality of life (QOL) of pathologic myopia patients. METHODS: A cross-sectional study was conducted using data of consecutive pathologic myopia patients (n = 200) and control subjects (n = 144). The influence of the disease on the daily life and the QOL of patients were evaluated using a self-rated questionnaire. The questionnaire covered the full range of daily life activity, including daily tasks depending on visual acuity, social and emotional handicaps, and cognition of disease, and the QOL of pathologic myopia patients. RESULTS: The functional status in daily life and the QOL of patients were reduced compared with control subjects. The influence of pathologic myopia on a patient's daily life was primarily the result of three major factors, handicap, disability, and support. All three factors correlated with the QOL, the degree of handicap having the strongest correlation. CONCLUSION: The functional status in daily life and the QOL of pathologic myopia patients were reduced; this decline in QOL was attributed to handicap and disability caused by the ocular disease.

Case report: indocyanine green dye leakage from retinal artery in branch retinal vein occlusion.

BACKGROUND: Little is known about retinal vascular lesions underlying hemorrhage in the acute phase of branch retinal vein occlusion (BRVO). CASE: A 64-year-old woman presented with a decrease in visual acuity of ten-day duration in her left eye. OBSERVATIONS: At the initial examination, her left fundus showed the typical appearance of BRVO, including retinal bleeding and soft exudates in the lower half of the fundus, after the arteriovenous crossing. Fluorescein angiography showed no detail in the retinal vessels, which were occluded by retinal bleeding. However, in the early phase of indocyanine green (ICG) angiography, ICG dye leaked from the retinal artery at a point proximal to the first bifurcation. In the late phase of ICG angiography, the dye pooled along the retinal artery in a fusiform fashion. One year after laser photocoagulation was performed in the area of the BRVO, ICG dye leakage from the retinal artery had completely disappeared. CONCLUSIONS: These findings suggest that the changes in the retina detected by ICG angiography may have been associated with the onset of BRVO. In patients with acute BRVO, ICG angiography may be used to evaluate retinal arterial lesions covered by hemorrhage and provide useful information.

Spontaneous involution of a large retinal arterial macroaneurysm.

BACKGROUND: Acquired retinal macroaneurysms are round dilatations of retinal arterioles that occur in the posterior fundus. They tend to rupture before they grow large and cause a visual decrease. The average diameter of macroaneurysms in the previous reports is 281 micrometer. METHODS: A 63-year-old man complained of a sudden decrease of visual acuity in the left eye. Fundus examination of his left eye revealed a large protruded mass, 2 disc diameters in size, at the first bifurcation of the inferotemporal retinal artery. Preretinal vitreous bleeding and serous retinal detachment were observed around the lesion. Indocyanine green (ICG) angiography showed this mass to be continuous with the inferotemporal retinal artery and ICG dye leaked from the retinal artery into the lumen of the mass, with pulsation. RESULTS: Six months later, the large macroaneurysm underwent spontaneous involution. CONCLUSION: As shown in this patient, retinal macroaneurysms may grow extremely large. ICG angiography was useful to diagnose this large retinal arterial macroaneurysm.

Bilateral large peripapillary venous and arterial loops.

BACKGROUND: Peripapillary loops of venous origin are extremely rare. CASE: A 55-year-old woman was referred to us for further examination of peripapillary vascular abnormalities. OBSERVATIONS: Fundus examination and fluorescein angiography clearly showed a venous and an arterial peripapillary loop in both her right and left fundi. The venous loop in the right eye was in a large hairpin configuration, extending into the retina about 1 disc diameter from the optic disc. Fluorescein angiography in the left eye revealed slow and irregular filling of dye into a venous loop that showed stasis of the bloodstream through the loop. Various retinal vascular abnormalities, including cilioretinal artery and triple branching of the retinal vein were also observed. CONCLUSION: The findings in this case of bilateral peripapillary venous and arterial loops and unilateral trifurcation of retinal vein suggest that there could be an association in the other retinal abnormalities. Periodic follow-up examinations seem necessary.

Indocyanine green angiographic findings of lacquer cracks in pathologic myopia.

Lacquer cracks are thought to represent healed mechanical breaks in the retinal pigment epithelium, Bruch's membrane, and choriocapillaris complex. In this study, we analyzed the indocyanine green (ICG) angiographic features of lacquer cracks and compared them with findings using fluorescein angiography. Complete ophthalmologic examinations, fluorescein angiography, and ICG angiography were performed in 29 consecutive patients (37 eyes) with lacquer cracks. Fluorescein angiograms of the cracks revealed linear hyperfluorescence in all 37 eyes. Using ICG angiography, we observed linear hypofluorescence in all 37 eyes. In 15 of 37 eyes, the length of the hypofluorescent lesion detected by ICG angiography was longer than the hyperfluorescent lesion observed by fluorescein angiography. In 17 of 37 eyes, more lacquer cracks were observed by ICG angiography than by fluorescein angiography. These findings indicate that ICG angiography can detect the development of the lesion more precisely, and may provide useful information for diagnosing pathologic myopia.

Zinn-Haller arterial ring observed by ICG angiography in high myopia.

AIMS: To delineate the entire Zinn-Haller arterial ring angiographically in vivo. METHODS: 382 highly myopic eyes (210 patients) with refractive errors greater than -8.25 D were examined using indocyanine green (ICG) videoangiography. A control group of 80 eyes (40 patients) had refractive errors within plano +/- 3D. RESULTS: The Zinn-Haller ring was visible in 206 of 382 highly myopic eyes (53.9%) by ICG angiography. Although only a part of the Zinn-Haller ring was visible in 162 of 206 eyes, in the remaining 44 eyes it was observed almost completely around the optic nerve head. No anastomotic channels between lateral and medial short posterior ciliary arteries were filled by ICG angiography. In 22 of the 44 eyes (50.0%) the Zinn-Haller ring was supplied by branches of the lateral and medial short posterior ciliary arteries; in seven eyes, it was supplied only by the lateral short posterior ciliary artery; and in seven eyes, it was supplied only by the medial short posterior ciliary artery. In none of the control subjects was the Zinn-Haller ring visible by ICG angiography. CONCLUSIONS: The Zinn-Haller ring observed by ICG angiography was not a complete collateral circle between lateral and medial posterior ciliary arteries. Also, the patterns in supply vessels to the Zinn-Haller ring varied. ICG angiography made possible the detailed observation of the Zinn-Haller ring in human eyes in vivo.

The long-term follow-up of a highly myopic patient with a macular vortex vein.

We followed a highly myopic patient with a macular vortex vein for 11 years. His refraction was -12D OU at age 10 years when the vein was first observed ophthalmoscopically in the left eye. Eleven years later, his myopia had progressed (4 diopters OD; 8 diopters OS), and the axial lengths were elongated (+1.8 mm OD; +2.7 mm OS). The macular vortex vein was dilated and tortuous. Indocyanine green angiography revealed the outflow route of this vein in the posterior pole, where both nasal and temporal posterior choroidal venous blood collected. Computed tomography showed that the vein left the eyeball directly and coursed along the optic nerve 5 mm posterior to the optic disc. A major collecting channel of posterior choroid outflow in some highly myopic eyes, a macular vortex vein may be formed at a relatively early age, and continue to enlarge, with elongation of axial length and progression of myopia.

Indocyanine green angiography of retrobulbar vascular structures in severe myopia.

PURPOSE: To evaluate angiographic findings of retrobulbar arteries and veins in severely myopic patients. METHODS: We examined 416 severely myopic eyes (213 patients) with refractive errors greater than -8.25 diopters using indocyanine green videoangiography. A control group of 74 eyes (37 patients) had refractive errors within plano +/- 3 diopters. Four severely myopic patients underwent computed tomographic angiography to identify the entire intraorbital course of retrobulbar veins. RESULTS: Of 416 severely myopic eyes, 231 (55.5%) exhibited retrobulbar arteries, which were tortuous and pulsatile behind the posterior pole of the globe. Retrobulbar arteries connected directly with choroidal arteries temporal to the macular area. In 17 of these 231 eyes, retrobulbar arteries were also observed nasal to the optic nerve head, continuous with the Zinn-Haller ring around the optic nerve head and directly connected with choroidal arteries. In 39 severely myopic eyes (31 patients), indocyanine green angiography disclosed retrobulbar veins, most of which coursed vertically just behind the posterior pole of the globe. These retrobulbar veins originated as an inferior vascular network of the inferior orbital vein and drained into the superior orbital vein in the upper orbit. CONCLUSION: Retrobulbar arteries observed in this study were temporal and nasal short posterior ciliary arteries. Only the lateral collateral vein, which was one of the collateral channels between the superior and inferior orbital veins, was visible in severely myopic eyes. Indocyanine green angiography is useful in evaluating retrobulbar vascular structure in severely myopic eyes.

Subretinal bleeding without choroidal neovascularization in pathologic myopia. A sign of new lacquer crack formation.

PURPOSE: The clinical significance of subretinal bleeding without choroidal neovascularization in pathologic myopia is unclear. Only two reports in the ophthalmic literature have demonstrated the clinical course of subretinal bleeding and have indicated that it might be a precursor of lacquer cracks. In this study, the authors observed the clinical course of subretinal bleeding in highly myopic eyes and studied this condition in relation to new lacquer crack formation. METHODS: The authors examined consecutively and prospectively 22 highly myopic eyes (19 patients) with subretinal bleeding. Indirect ophthalmoscopy and fluorescein fundus angiography were performed in all patients. Indocyanine green (ICG) angiography could be performed in three patients. The follow-up period ranged from 6 to 198 months (mean, 61.3 months). RESULTS: In 17 of 22 eyes, lacquer cracks appeared at the site of previous subretinal bleeding. The period for the formation of new lacquer cracks after the onset of the bleeding ranged from 2 to 6 months (mean, 4.0 months). In one patient, ICG angiography revealed linear hypofluorescence, indicating a ruptured Bruch's membrane at the onset of subretinal bleeding. CONCLUSION: A rupture of Bruch's membrane and choriocapillaris complex results in subretinal bleeding, which is the first process of new lacquer crack formation. Atrophy of the overlying pigment epithelium and further scar formation results in the development of a lacquer crack.

The progression of lacquer cracks in pathologic myopia.

PURPOSE: Lacquer cracks are found in the posterior fundus of 4.3% of highly myopic eyes. They represent healed and mechanical breaks of the retinal pigment epithelium, Bruch's membrane, and choriocapillaris complex. This prospective study examined the progressive course and angiographic characteristics of transitional changes in highly myopic eyes with lacquer cracks. METHODS: The authors studied 66 eyes (53 patients with lacquer cracks, using general ocular examinations and fluorescein angiography once every 3 to 12 months. Follow-up ranged from 7 to 243 months (average, 72.8 months). RESULTS: The lacquer cracks progressed in 37 eyes (56.1%). Of these 37 eyes, the number of lacquer cracks increased in 14 eyes and turned into other myopic fundus changes in 25 eyes. These changes included patchy atrophy, diffuse atrophy, and choroidal hemorrhage with neovascular membrane (Fuchs' spot). Fluorescein angiography showed patchy atrophy beginning with a small hypofluorescent area at the peripheral end of the lacquer cracks. CONCLUSION: A high incidence of lacquer cracks progressed into advanced fundus changes during a mean follow-up period of 6 years. Even faint lacquer cracks may characterize an unfavorable prognostic course, leading to macular pathology in patients with pathologic myopia.

Posterior routes of choroidal blood outflow in high myopia.

PURPOSE: A few reports in the ophthalmic literature have described choroidal blood outflow through posterior routes. Most of the patients reported were highly myopic; therefore, a correlation between such posterior routes and high myopia has been suspected. The authors examined highly myopic eyes using indocyanine green (ICG) videoangiography and investigated the prevalence and clinical significance of posterior routes in them. METHODS: The authors examined 255 highly myopic eyes (146 patients) using ICG videoangiography. All had refractive errors greater than--8.25 diopters (D). They also examined a control group consisting of 42 eyes (26 patients) that had refractive errors within +/- 3D. RESULTS: Of 255 highly myopic eyes, 61 (23.9%) had choroidal blood outflow through posterior routes. These routes were classified by type of vein according to its penetration site. One drained into the margin of the optic nerve head, and the other penetrated the sclera near the macula. However, only 1 of the 42 eyes (2.4%) in the control group showed choroidal outflow by a posterior route. The prevalence of posterior routes was significantly higher in the highly myopic eyes than in the control group (P < 0.05). CONCLUSION: Posterior routes of choroidal blood outflow were observed in nearly 25% of highly myopic eyes. These vessels appear to be one of the major routes of posterior choroidal outflow in highly myopic eyes.