Inner Segment And Outer Segment Research Articles

Phenotype Heterogeneity and the Association Between Visual Acuity and Outer Retinal Structure in a Cohort of Chinese X-Linked Juvenile Retinoschisis Patients

Purpose: X-linked juvenile retinoschisis (XLRS), caused by mutations in the RS1 gene, is an X-linked recessive inherited disease that typically involves both eyes in the first 2 decades of life. Recently, the phenotype heterogeneity of this condition has drawn increasing attention. We reported various phenotypes caused by RS1 gene mutations in eleven patients from ten Chinese families. Methods: Data on the medical history of the patients from ten Han families of central China were collected. Ophthalmic examinations including best-corrected visual acuity (BCVA), fundus photography, ultra-wide-angle sweep source optical coherence tomography (SS-OCT), and electroretinography (ERG) were performed. Adaptive optics (AO) images were acquired to evaluate the cone photoreceptor mosaic when applicable. Venous blood of the probands and their family members was collected, and DNA was subjected to sequencing based on next-generation sequencing with a custom-designed targeted gene panel PS400 for inherited retinal diseases. Validation was performed by Sanger sequencing and cosegregation. Pathogenicity was determined in accordance with the American College of Medical Genetics and Genomics (ACMG) guidelines. Results: Ten RS1 mutations, including eight missense mutations and two terminator mutations, were identified in 10 XLRS families. c.657C > A (p.C219X) was a novel mutation in this cohort. These patients showed a variety of clinical phenotypes, including fovea schisis, bullous retinoschisis, and macular or peripheral atrophy. Fifteen eyes of eight patients exhibited macular retinoschisis, and twelve eyes of seven patients exhibited peripheral retinoschisis. In addition, three patients showed asymmetrical fundus manifestations. Of importance, three patients without macular retinoschisis were misdiagnosed until genetic testing results were obtained. AO showed a decrease in cone density and loss of regularity in the cystic schisis macular of XLRS. Furthermore, the BCVA was associated with the photoreceptor inner segment and outer segment (IS/OS) thickness. Conclusion: With complicated clinical manifestations, a considerable portion of XLRS patients may present various phenotypes. It should be noted that asymmetry in fundus appearance in both eyes could lead to misdiagnosis easily. Thus, genetic testing is crucial for making a final diagnosis in those patients who are suspected of having amblyopia, bilateral or unilateral macular atrophy, or conditions presenting an asymmetric fundus appearance. In addition, the residual cone photoreceptor structure was critical for the maintenance of useful vision.

Effects of Indocyanine Green Staining on the Recovery of Visual Acuity and Macular Morphology after Macular Hole Surgery

Purpose: To evaluate whether indocyanine green (ICG)-assisted internal limiting membrane peeling affects visual outcome and macular morphologic changes in spectral-domain optical coherence tomography images after macular hole (MH) surgery. Methods: A retrospective analysis was performed of 34 eyes in 34 patients who had undergone surgical treatment for MH. Best-corrected visual acuity (BCVA) and optical coherence tomography parameters including central foveal thickness, length of the external limiting membrane (ELM) defect, and length of the inner segment and outer segment (IS/OS) defect were analyzed pre- and postoperatively. Results: The eyes were divided into 2 groups based on ICG use (ICG+/-). The changes in BCVA did not differ significantly between the 2 groups at 6 months. However, the ICG+ group had poorer changes compared with the ICG- group at 1 and 3 months (p = 0.038, p = 0.012, respectively). Central foveal thickness and ELM defect did not differ between the 2 groups at each period. The IS/OS defect in the ICG+ group was significantly greater at 1 and 3 months than that in the ICG- group (p = 0.026, p = 0.048, respectively). Conclusions: ICG staining may affect the recovery process of macular morphology and visual acuity in the first several months after MH surgery.

Preferential Hyperacuity Perimeter and Prognostic Factors for Metamorphopsia After Idiopathic Epiretinal Membrane Surgery

To document changes in metamorphopsia via preferential hyperacuity perimeter and to identify prognostic factors related to favorable metamorphopsia outcome after idiopathic epiretinal membrane surgery. Prospective, consecutive, interventional case series. We prospectively included 29 eyes of 27 patients who underwent successful vitrectomy for idiopathic epiretinal membrane. All eyes underwent examinations before surgery and at 2weeks and 1, 3, and 6months after surgery. Metamorphopsia was assessed by using a preferential hyperacuity perimeter. Several clinical factors were analyzed to reveal relationships with final metamorphopsia outcome, including the duration of symptoms, best-corrected visual acuity, and spectral-domain optical coherence tomography findings. Spectral-domain optical coherence tomography findings included assessment of central foveal thickness, and the integrity of the photoreceptor inner segment and outer segment (IS/OS) junction. At baseline, preferential hyperacuity perimeter detected areas of distortion in 15 eyes (51.7%). At 6months after surgery, there was significant reduction in metamorphopsia (P= .001), which was paralleled with significant improvement of best-corrected visual acuity and reduction of central foveal thickness (P < .001). At 6months after surgery, the degree of metamorphopsia was related significantly to the severity of preoperative metamorphopsia and central foveal thickness at baseline (ρ= 0.856; P < .001; ρ= 0.412; P= .027; respectively). Eyes with broadly disrupted IS/OS junction of more than 200μm before surgery revealed significantly poorer postoperative metamorphopsia than those with intact or narrowly disrupted IS/OS junction (P= .001). However, duration of symptoms and baseline best-corrected visual acuity were not correlated with final metamorphopsia (P= .625 and P= .052, respectively). Significant reduction of metamorphopsia paralleled the improvement of best-corrected visual acuity and central foveal thickness until 6months after idiopathic epiretinal membrane surgery. The significant predictors for postoperative metamorphopsia outcome were the degree of preoperative metamorphopsia, central foveal thickness, and the photoreceptor IS/OS junction integrity at baseline.

Optical coherence tomography features of Best vitelliform macular dystrophy at different stages

[Objective] To observe the optical coherence tomography (OCT) features of Best vitellilorm macular dystrophy (BVMD) at different stages.[Methods] Twenty-eight BVMD patients (56eyes) were enrolled in this study.All the patients were examined for visual acuity,slit-lamp microscopy,direct ophthalmoscope,fundus photography,electrooculogram,fundus fluorescein angiography (FFA) and OCT.Fifty-six eyes were classified into stage 0 (eight eyes) 、Ⅰ (two eyes)、Ⅱ (10 eyes)、Ⅱ a (12 eyes)、Ⅲ(six eyes) 、Ⅳa (six eyes)、Ⅳb (five eyes) and Ⅳc (seven eyes) accordingly.The OCT features of BVMD at different stages were observed.[Results] The OCT results showed that the macular area was normal in eyes of stage 0; disturbance of retinal pigment epithelium (RPE) and subretinal hyporeflective area were found in eyes of stage Ⅰ; the location of the yellowish material between RPE and the inner segment and outer segment (IS/OS) with normal appearance in RPE and IS/OS interface were found in eyes of stage Ⅱ.In all the other progressing stages from Ⅱ a、Ⅲ and Ⅳ,the vitelliform material appeared as a thicker highly reflective lesion located between the outer nuclear layer and RPE layer,usually accompanied by optical hyporeflective lesion.Images of stage Ⅳ c were in similar appearance besides edema of retina.OCT images of Ⅳ b stage were demonstrated atrophy of retinal layer and IS/OS loss with fibrosis.[Conclusion]s OCT demonstrated the location of the yellowish material between RPE and IS/OS.Optical hyporeflective lesion between the outer nuclear layer and RPE layer accompanied thicker highly reflected lesion might be the characteristic image in stages Ⅱ a to Ⅳ of BVMD. Key words: Macular degeneration/diagnosis; Tomography; optical coherence; Diagnostic imaging

High-Resolution In Vivo Imaging in Achromatopsia

To characterize the retinal changes in patients with achromatopsia using an ultrahigh-resolution (UHR) spectral-domain optical coherence tomography (OCT) to examine how human achromatopsia corresponds to its animal model. Comparative case series. Ultrahigh-resolution OCT (Copernicus; OPTOPOL Technology S.A., Zawiercie, Poland; 3-μm axial resolution) was used to obtain scans from 13 patients (26 eyes) with achromatopsia and from 20 controls (40 eyes). A 3-dimensional scan program (743×75; A×B scan) sampling a 7×7-mm retinal area centered at the fovea was used to obtain tomograms of the fovea. Individual B-scans at the fovea were exported and analyzed using ImageJ (Wayne Rasband, National Institute of Health) for reflectance profiles and morphologic abnormalities. Gross morphologic changes in OCT were characterized. Specifically, inner segment and outer segment (IS/OS) junction and cone outer segment tip (COST) disruption was noted. Using the reflectance profiles, foveal depth, thickness of the outer nuclear layer (ONL), and retinal thickness (RT) were measured. A characteristic so-called punched out hyporeflective zone (HRZ) was noted in 7 of 13 patients; this was age-dependent (P = 0.001). The area of the HRZ was asymmetric with the nasal area being significantly greater than the temporal area (P = 0.002). In all patients, there was disruption of the IS/OS junction at the foveal or parafoveal regions, or both. Five of 13 patients also had a disrupted COST reflectivity. There was significant (P = 1.1×10(-6)) ONL thinning in the achromats compared with controls, which was age-dependent (P = 0.0002). Foveal maldevelopment was seen in 9 of 13 patients. The achromats also had a significantly reduced foveal depth (P = 7.7×10(-6)) and RT (P = 1.46×10(-9)) compared with controls. A range of signs in achromatopsia are described that can be detected using UHR OCT. The IS/OS junction and COST reflectivity disruption and presence of HRZ and ONL thinning are signs of cone photoreceptor degeneration. The latter 2 are age-dependent, which suggests that achromatopsia is a progressive disorder. In addition, foveal maldevelopment is described; this represents a fetal developmental defect linked to cone photoreceptor degeneration.

Correlation of fundus autofluorescence with photoreceptor morphology and functional changes in eyes with retinitis pigmentosa

To assess and correlate fundus autofluorescence (FAF) characteristics with photoreceptor morphology and functional features in eyes with retinitis pigmentosa (RP). Thirty-four eyes of 17 patients with RP were examined. We compared FAF images obtained by confocal scanning laser ophthalmoscopy with Spectral-domain optical coherence tomography (SD-OCT) and retinal function assessed by microperimetry. Normal FAF surrounded by a ring of increased FAF at the macular area was detected in 32 (94%) eyes. The diameter of the normal FAF was correlated significantly with the preserved area of the photoreceptor inner segment and outer segment (IS/OS) junction on SD-OCT (R=0.939, p<0.001). The area outside the ring was associated with loss of IS/OS junction and external limiting membrane (ELM). The ring of increased FAF demarcated the border between the central retina with preservation of the IS/OS junction and ELM, and the adjacent eccentric retina with loss of these bands. In two eyes of one patient, there was no preservation of normal FAF at the macula and the photoreceptor IS/OS junction was not detected on SD-OCT. The mean retinal sensitivity derived from microperimetry was correlated significantly with the area of normal FAF (R=0.929, p=0.007) and the preserved area of the IS/OS junction (R=0.851, p=0.032). Ten eyes had progressive reduction in size of the normal FAF inside the ring accompanied by decreased area of preserved IS/OS during 3.1 years. FAF appears to reflect the integrity of the photoreceptor layer. It may serve as a secondary outcome measure for novel therapeutic strategies for RP.

Analysis of spectral domain optical coherence tomography findings in occult macular dystrophy

To describe findings of spectral domain optical coherence tomography (SD-OCT) in the diagnosis of occult macular dystrophy (OMD). Five visually disturbed patients who had shown normal findings in full field electroretinogram (ERG), fundus photography and fluorescein angiography but abnormal findings in multifocal ERG had undergone SD-OCT. The morphologic changes in retina and macular thickness were detected and imaged by SD-OCT. We analysed the results of SD-OCT including macular thickness, inner segment and outer segment (IS/OS) boundary and external limiting membrane (ELM). Mean age was 41.6 (22-63) in three male and two female patients in this study. Mean central foveal thickness was 142.9 (76-161) μm. All patients had shown decreased bowing of IS/OS boundary, and five of nine eyes were noted with disrupted IS/OS boundary of the photoreceptors according to SD-OCT. The interruption of external limiting membrane was noted in three of nine eyes. Spectral domain optical coherence tomography findings are useful in diagnosing OMD. Morphologic changes of the retina including deformity of the OS/IS boundary of the photoreceptors, disruption of the ELM and decreased foveal thickness may be important characteristics to consider when determining the pathophysiology and diagnosing criteria of OMD.

Spectral-Domain Optical Coherence Tomography for Monitoring Epiretinal Membrane Surgery

To assess prognostic factors in epiretinal membrane (ERM) surgery using spectral-domain (SD) optical coherence tomography (OCT). Prospective, interventional case series. Forty-one patients. Patients with a diagnosis of ERM were examined with spectral-domain and time-domain (TD) OCT before and after surgery. Main outcome measures were functional results and predefined OCT patterns. Cofactors analyzed were the type of ERM, the duration and grading of subjective metamorphopsia, simultaneous cataract surgery, the type of dyes used, the duration of surgery, gender, and age. A multivariate regression analysis was performed. Thirty-nine patients (95%) showed an improved or stable best-corrected distance visual acuity (DVA) at 3 months, whereas 36 patients (88%) showed an improved or stable best-corrected near visual acuity (NVA) at 3 months. Significant correlations (P>0.4) were found between the course of central retinal thickness (CRT) assessed using SD OCT and TD OCT (P<0.02). No clinically relevant correlations (P<0.3) were seen between CRT and VA (P>0.1). Baseline DVA and NVA were found to be significant prognostic values for the postoperative decrease in CRT in both OCT systems (P<0.04) as well as for the visual outcomes (P<0.007) at 3 months. In addition, the integrity of the junction between the photoreceptor inner segment and outer segment (IS/OS) significantly influenced the visual outcomes at 3 months (P<0.038). The baseline profile of the internal limiting membrane (ILM) significantly influenced the NVA at 3 months (P<0.009), whereas the postoperative foveal contour significantly influenced the DVA at 3 months (P<0.025). The type of ERM, subjective metamorphopsia, simultaneous cataract surgery, the type of dyes used, the duration of surgery, gender, or age had no significant influence on patient outcome (P>0.05). Compared with TD OCT, SD OCT allowed for a more precise differentiation between the ERM and the retinal surface and for a better evaluation of the IS/OS line. Besides the baseline VA, the integrity of the IS/OS line, better visualized by SD OCT, can be used to predict the functional outcomes after surgery. Additionally, analyzing the ILM profile and the foveal contour may help to understand limited visual outcomes after surgery. The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Restoration of Photoreceptor Outer Segment after Vitrectomy for Retinal Detachment

To report photoreceptor restoration and visual outcomes after vitrectomy for retinal detachment. Retrospective, observational case series. We prospectively studied the tomographic features of reattached retinas in 20 eyes with a macula-off rhegmatogenous retinal detachment using spectral-domain optical coherence tomography 1, 3, and 6 months after 3-port vitrectomy with SF(6) gas tamponade. All eyes were examined more than 3 months after surgery. The optical coherence tomography foveal findings were classified as a disrupted inner segment and outer segment (IS/OS) line, a residual foveal detachment, and a continuous IS/OS line. A disrupted IS/OS line was seen in 11 eyes (55%) at 1 month and in 8 eyes (40%) at 3 months, a foveal detachment was seen in 8 eyes (40%) at 1 month and in 7 eyes (35%) at 3 months, and a continuous IS/OS line was seen in 1 eye (5%) at 1 month and in 5 eyes (25%) at 3 months. In 18 eyes followed up for 6 months, optical coherence tomography showed a disrupted IS/OS line in 3 eyes (17%), a foveal detachment in 6 eyes (33%), and a continuous IS/OS line in 9 eyes (50%). The mean best-corrected visual acuities at 1 and 6 months were 0.26 and 0.16 with a disrupted IS/OS line, 0.60 and 0.95 with a foveal detachment, and 0.8 and 0.95 with a continuous IS/OS line. The mean best-corrected visual acuity was significantly (P < .0001) lower with a disrupted IS/OS line compared with the other formations at 6 months. The IS/OS line at the fovea recovered gradually after surgery. The postoperative visual acuity was correlated with a restored IS/OS line.

Association between Foveal Photoreceptor Integrity and Visual Outcome in Neovascular Age-related Macular Degeneration

To evaluate the correlation between visual outcome and foveal photoreceptor integrity after successful treatment of eyes with neovascular age-related macular degeneration (AMD). Retrospective chart review. We retrospectively studied the medical records of 51 eyes of 51 patients with neovascular AMD who were treated successfully with photodynamic therapy (PDT). All eyes were followed-up for more than 24 months after the initial treatment. Using spectral-domain optical coherence tomography, the status of the inner segment and outer segment (IS/OS) photoreceptor junction was assessed as a hallmark of the integrity of the foveal photoreceptor layer. At the final visit, no eyes showed an exudative change. A complete or discontinuous IS/OS line was detected beneath the fovea in 8 (15.7%) and 25 (29.4%) eyes, respectively, whereas 28 (54.9%) had no IS/OS line. Eyes with a continuous or discontinuous IS/OS line beneath the fovea had better final visual acuity (VA) than did eyes without an IS/OS line (P < .001, respectively). Of the 51 eyes, 36 showed polypoidal choroidal vasculopathy (PCV), whereas 15 were diagnosed as having typical AMD without PCV. Visual outcome was significantly better in eyes with PCV (P = .026). Most eyes (13/15; 86.7%) with typical AMD had no IS/OS line at the final visit, whereas only 13 (36.1%) of the 36 eyes with PCV had no IS/OS line beneath the fovea. Integrity of the photoreceptor layer beneath the fovea is associated with the final VA in neovascular AMD after successful PDT.

High-Definition Optical Coherence Tomography Features in Vitelliform Macular Dystrophy

To correlate high-definition optical coherence tomography (HD OCT) and fundus examination findings at different phases of vitelliform macular dystrophy and to determine the anatomic location of vitelliform material. Prospective, noncomparative, observational case series. A complete ophthalmologic examination, including fundus biomicroscopy and HD OCT, was performed in 11 consecutive patients with a diagnosis of vitelliform macular dystrophy. Using HD OCT, we were able to demonstrate for the first time the presence of previtelliform lesions, characterized by a thicker layer between the retinal pigment epithelium (RPE) and the inner segment and outer segment (IS/OS) interface. At this stage, a normal-appearing RPE and IS/OS interface were found in two of four eyes. In all progressive stages from the vitelliform to the vitelliruptive, the vitelliform material was visualized by HD OCT as an highly reflective lesion located between the hyporeflective outer nuclear layer and the hyperreflective RPE layer, associated or not to an optically empty lesion. At these stages, a disrupted IS/OS interface and an almost normal appearance of all major intraretinal layers was detected. At the vitelliruptive and atrophic stages, on some parts, the HD OCT scan revealed hyperreflective mottling on the RPE layer, probably representing areas of focal RPE hypertrophy. The atrophic stage and the fibrotic stage were characterized by thinning of all the retinal layers and diffuse loss of the IS/OS interface. In our series, mean best-corrected visual acuity impairment showed a statistically significant correlation to the presence of focal disruption or diffuse loss of the IS/OS interface (P = .002), as well as to a more advanced stage of the disease (P = .01). A more advanced stage of the disease showed a strong statistically significant correlation to the presence of diffuse loss of the IS/OS interface (P < .001). Based on the HD OCT findings, we hypothesize that early changes in vitelliform macular dystrophy involve the layer between the RPE and the IS/OS interface, first with accumulation of material beneath the sensory retina, and then with disruption and attenuation of IS and OS; late changes seem to affect the RPE, which undergoes hypertrophy, disruption, and attenuation.