Optical coherence tomography biomarkers DROL, PROS, SND, hyperreflective walls of foveal cystoid spaces as predictors of central macular thickness and visual acuity in diabetic macular edema treated with intravitreal ranibizumab.

PURPOSE: This study aims to establish DROL (disruption of retinal outer layers), PROS (photoreceptor outer segment length), SND (subfoveal neuroretinal detachment), and hyperreflective walls of foveal cystoid spaces (HRW) as optical coherence tomography (OCT) biomarkers and predictors of central macular thickness (CMT) and visual acuity in diabetic macular edema (DME) treated with intravitreal ranibizumab (IVR). METHODS: In this prospective, interventional study performed at a tertiary care center over a span of 1 year from December 2021 to December 2022, 50 eyes of 46 patients of DME were included. Visual acuity and spectral domain OCT imaging were performed at baseline. Using inbuilt calipers on SD-OCT, the horizontal extent of DROL and the vertical extent of PROS were measured manually. SND and HRW were assessed qualitatively. IVR was administered and patients were followed up at 4, 8, and 12 weeks. RESULTS: The eyes without DROL had statistically significant (P < 0.05) lesser CMT and better BCVA (best-corrected visual acuity) (P < 0.05) after pro re nata injection of IVR. There was a positive correlation between the extent of baseline DROL with final CMT (P < 0.05) and final logMAR BCVA (P > 0.05), whereas negative correlation with the extent of baseline PROS with final CMT (P < 0.05) and final logMAR BCVA (P > 0.05). The presence of HRW and SND predicted non-resolution of CMT and worse visual acuity after treatment with IVR in DME. CONCLUSION: DROL, PROS, SND, and hyperreflective walls of foveal cystoid spaces may be utilized as qualitative as well as quantitative biomarkers to predict the post-treatment CMT and visual acuity in DME.

In vivo evaluation of outer retinal function and structure after retrobulbar optic nerve crush by lateral orbitotomy in goats.

Large animal model of optic nerve crush (ONC) plays an important role in translating novel therapeutic strategies developed in rodent model to clinical application. Due to the poor accessibility of the optic nerve (ON) in humans and large animals, lateral orbitotomy is needed to expose the retrobulbar ON. This study was to explore the effects of ONC and ON exposure with lateral orbitotomy (sham surgery) on the outer retinal function and structure in goats by using standard flash electroretinogram (FERG) and spectral-domain optical coherence tomography (SD-OCT). We found that ONC led to a transient reduction in FERG amplitudes at 1 week post injury (wpi), which recovered gradually over 2 months afterwards. Sham surgery alone also caused a similar pattern of amplitude reduction in FERG, although not as significantly as ONC did. Transient outer retinal thickening following ONC occurred at 4 wpi (when progressive thinning of the ganglion cell complex began), peaked at 8 wpi, then recovered gradually at 12 wpi. In contrast, outer retinal thickness remained unchanged statistically 3 months after sham surgery. Fundus fluorescein angiography showed that neither ONC nor ON exposure with lateral orbitotomy significantly caused any significant delay or absence of central retinal vascular filling. In summary, ONC with lateral orbitotomy affects outer retinal function and structure transiently.

Gene Correction Recovers Phagocytosis in Retinal Pigment Epithelium Derived from Retinitis Pigmentosa-Human-Induced Pluripotent Stem Cells.

Hereditary retinal dystrophies (HRD) represent a significant cause of blindness, affecting mostly retinal pigment epithelium (RPE) and photoreceptors (PRs), and currently suffer from a lack of effective treatments. Highly specialized RPE and PR cells interact mutually in the functional retina, therefore primary HRD affecting one cell type leading to a secondary HRD in the other cells. Phagocytosis is one of the primary functions of the RPE and studies have discovered that mutations in the phagocytosis-associated gene Mer tyrosine kinase receptor (MERTK) lead to primary RPE dystrophy. Treatment strategies for this rare disease include the replacement of diseased RPE with healthy autologous RPE to prevent PR degeneration. The generation and directed differentiation of patient-derived human-induced pluripotent stem cells (hiPSCs) may provide a means to generate autologous therapeutically-relevant adult cells, including RPE and PR. However, the continued presence of the MERTK gene mutation in patient-derived hiPSCs represents a significant drawback. Recently, we reported the generation of a hiPSC model of MERTK-associated Retinitis Pigmentosa (RP) that recapitulates disease phenotype and the subsequent creation of gene-corrected RP-hiPSCs using Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/Cas9. In this study, we differentiated gene-corrected RP-hiPSCs into RPE and found that these cells had recovered both wild-type MERTK protein expression and the lost phagocytosis of fluorescently-labeled photoreceptor outer segments observed in uncorrected RP-hiPSC-RPE. These findings provide proof-of-principle for the utility of gene-corrected hiPSCs as an unlimited cell source for personalized cell therapy of rare vision disorders.

BACILLARY LAYER DETACHMENT BECAUSE OF MACULAR NEOVASCULARIZATION.

PURPOSE: To describe the clinical and multimodal imaging features of bacillary layer detachment (BD), and its response to intravitreal anti-vascular endothelial growth factor therapy, in eyes with macular neovascularization. METHODS: Retrospective, observational case series of 14 eyes (14 patients, 7 men) imaged with eyes (14 patients, 7 men) were imaged with spectral-domain optical coherence tomography, and either fluorescein angiography or optical coherence tomography angiography. Therapeutic response was monitored with serial imaging and best-corrected visual acuity assessments. RESULTS: The mean age was 75 ± 13 (range: 45-96) years, with mean follow-up duration of 27 ± 21 (range: 1-56) months. Neovascular age-related macular degeneration was found in 71% (10/14) eyes. Type 2 macular neovascularization lesions were associated with BD in all 14 eyes. Subretinal hemorrhage was noted in 79% (11/14) eyes. BD promptly resolved after intravitreal antivascular endothelial growth factor therapy in all eyes. The baseline best-corrected visual acuity improved from logarithm of the minimum angle of resolution 0.84 ± 0.32 (Snellen equivalent 20/138) to logarithm of the minimum angle of resolution 0.48 ± 0.31 (Snellen equivalent 20/60) at the last follow-up, with treatment of the macular neovascularization. CONCLUSION: Type 2 macular neovascularization and subretinal hemorrhage are associated with BDs, which may be due to a rapid influx of exudative fluid into the potential space between the external limiting membrane and ellipsoid zone. Intravitreal antivascular endothelial growth factor therapy results in rapid resolution of BDs and visual improvement in most eyes.

OUTER RETINAL TUBULATION MAY RESULT FROM FIBROSED TYPE 2 NEOVASCULARIZATION: Clinical Observations and Model of Pathogenesis.

PURPOSE: To investigate the role of Type 2 macular neovascularization with subsequent subretinal fibrosis in the pathogenesis of outer retinal tubulation (ORT). METHODS: We conducted a retrospective cohort study of patients with stabilized inactive exudative macular degeneration who had been treated with intravitreal injections of antivascular endothelial growth factor agents. Baseline fluorescein and optical coherence tomography images were included. Macular neovascularizations (MNVs) were classified by type and size. Consecutive optical coherence tomography images analyzed for ORT development. RESULTS: One hundred forty-four eyes of 134 patients were included in this study. Sixty eyes presented with pure Type 1 MNV. Eighty-four eyes presented with some Type 2 component of MNV. In total, evidence of ORT is shown in 55 (38%) eyes. In the Type 1 group, 6.7% developed ORT. Outer retinal tubulation developed in 61% of eyes with some Type 2 component of the MNV. Among eyes that developed ORT, 92.7% presented with some Type 2 component. In a multivariate analysis, Type 2 membranes on optical coherence tomography (22.2 [6.1-80.8]; P < 0.001), larger MNV size {>1 DA (5.1 [1.1-24.2]; P = 0.041) and >1.5 DA (9.0 [1.8-44.0]; P = 0.007)}, and presence of subretinal fibrovascular material (3.1 [1.1-8.5]; P = < 0.03) are associated with higher odds of ORT formation. Once the ORT is formed, fibrosis was observed directly underlying the ORT on SD-optical coherence tomography in 70.9% of cases. CONCLUSION: Type 2 membranes at presentation predict ORT formation. Fibrosis often underlies ORT. This suggests that contraction of Type 2 MNV-derived fibrosis may be important in ORT formation.

EN FACE IMAGING OF OUTER RETINAL PATHOLOGY AFTER RETINAL DETACHMENT.

PURPOSE: To explore the potentials of multicolor (MC) confocal scanning laser ophthalmoscopy (cSLO) to detect structural retinal pathology after macula-off rhegmatogenous retinal detachment (RRD) and to describe their appearances. METHODS: Thirty MC cSLO images of 30 eyes after RRD repair were prospectively studied for the presence of RRD-related pathology. All MC cSLO findings were verified using swept source optical coherence tomography. Positive percent agreements were calculated using swept source optical coherence tomography as reference. RESULTS: Eight RRD-related structural pathologies were identified and characterized: ellipsoid zone (EZ) disruption, foveal EZ rosette, outer retinal fold, retinal detachment line, subretinal fluid blebs, subretinal fluid layer, retinal striae, and intraretinal cysts. Multicolor cSLO positive percent agreements were as follows: EZ disruption: 79%, foveal EZ rosette: 73%, outer retinal fold: 67%, retinal detachment line: 84%, subretinal fluid blebs: 0.70%, subretinal fluid layer: 50%, intraretinal cysts: 60%, and retinal striae: 100%. CONCLUSION: En face MC cSLO imaging detected and delineated RRD-related structural pathology in high agreement with cross-sectional swept source optical coherence tomography and can supplement optical coherence tomography in the documentation and monitoring of outer retinal remodeling processes after macula-off RRD. Foveal EZ rosette is a new finding of the foveal EZ.

ATTENUATION OUTER RETINAL BANDS ON OPTICAL COHERENCE TOMOGRAPHY FOLLOWING MACULAR EDEMA: A Possible Manifestation of Photoreceptor Misalignment.

PURPOSE: Macular edema is a common retinal disease which may leave important anatomical and functional sequelaes. Directional fundus imaging consists of comparing on- and off-axis images to reveal angle-dependent reflectance properties of fundus structures, which may be related to misaligned photoreceptors. Here, we analyzed directional optical coherence tomography (OCT) and flood-illumination adaptive optics ophthalmoscopy images to detect evidence of misaligned photoreceptors following macular edema. METHODS: Transversal, observational study. Nine patients having recovered a normal macular profile after macular edema due to retinal vein occlusion were included. For each patient, a reference OCT scan (i.e., with the incident beam normal to the fovea) was acquired, and off-axis scans were then acquired by laterally shifting the entry pupil. In addition, in four of these eyes, directional adaptive optics ophthalmoscopy documented the directional variations of cone metrics. RESULTS: Included patients comprised two women and seven men (age range, 19-76 years). Reference OCT scans showed patchy attenuation of the cone outer segment tips and to a lesser extent of the inner segment/outer segment lines in all, but two eyes; these. Increased intensity of the cone outer segment tips and inner segment/outer segment lines could be observed on off-axis scans. Accordingly, fusion images showed 66% average reduction of the length of cone outer segment tips attenuation. In two cases, although reference scans showed continuity of outer bands, focal attenuation was evidenced in off-axis images. Directional adaptive optics ophthalmoscopy imaging showed a strong directional variability of cone counts in these areas, ranging from near absence to roughly two-third of reference values. In each case, directional variations of cone counts paralleled those of the reflectance of outer bands. CONCLUSION: After macular edema, focal attenuations of the inner segment/outer segment and of the cone outer segment tips lines may be present on OCT. These areas may show a strong directional variability by both OCT and adaptive optics ophthalmoscopy, suggesting that misaligned photoreceptor outer segments contribute to such features. The evaluation of outer retinal damage following macular edema should therefore take into account the optical Stiles-Crawford effect to disambiguate missing from misaligned cones.

Outer retinal hyperreflective deposits (ORYD): a new OCT feature in naïve diabetic macular oedema after PPV with ILM peeling.

AIMS: We aimed to investigate a novel optical coherence tomography (OCT) finding of outer retinal hyperreflective deposits (ORYDs) in patients with naïve diabetic macular oedema (DMO) seen after small gauge pars plana vitrectomy (PPV) with internal limiting membrane (ILM) peeling. Furthermore, we evaluated the predictive value of ORYD for visual outcome over 24 months follow-up. METHODS: Retrospective cohort study including 111 eyes from 111 patients with naïve DMO treated by PPV and ILM peeling with a follow-up of 24 months. OCT scans were analysed for the presence of ORYD 1 week and 1, 6, 12, 18 and 24 months after surgery. Change in baseline best-corrected visual acuity (BCVA) and central subfoveal thickness (CST) after surgery were measured over the follow-up period. Presence of ORYD was correlated with baseline characteristics and BCVA after 24 months. RESULTS: Hundred and eleven eyes from 111 patients were included (mean age 67.5±14.8 years). ORYD was identified in the outer plexiform layer as hyperreflective deposits in 92 patients (82.8%) 7 days after surgery but it was not present before surgery. There was a significant reduction in the presence of ORYD. After 24 months ORYD disappeared in all cases (p<0.001). CONCLUSIONS: We describe a novel OCT feature of ORYD present in the early postoperative phase in the majority of patients after PPV with ILM peeling for naïve DMO, disappearing over the postoperative course. These deposits might be a result of sudden desinflammation and could shed new light on the process of DMO resolution after operative intervention.

Multimodal Imaging of Punctate Outer Retinal Toxoplasmosis.

BACKGROUND AND OBJECTIVE: To describe the multimodal imaging characteristics associated with punctate outer retinal toxoplasmosis (PORT). PATIENTS AND METHODS: Multicenter, retrospective, observational case series of three patients who presented with PORT. Multimodal imaging was reviewed including optical coherence tomography (OCT), fundus autofluorescence, optical coherence tomography angiography, and conventional dye-based angiography. RESULTS: Patient ages ranged from 13 years to 55 years. Each patient had multiple white, punctate outer retinal lesions in the affected eye at initial diagnosis. OCT showed both inner and outer retinal changes, including disruption of the ellipsoid and interdigitation zones and retinal pigment epithelium/Bruch's membrane complex, as well as punctate, preretinal, hyperreflective lesions at the vitreoretinal interface, which regressed with treatment. CONCLUSION: Multimodal imaging is useful in diagnosing and monitoring treatment response in PORT, an uncommon presentation of ocular toxoplasmosis that must be differentiated from white dot syndromes or other causes of unilateral retinitis. [Ophthalmic Surg Lasers Imaging Retina. 2019;50:281-287.].

FUNCTIONAL AND ANATOMICAL SIGNIFICANCE OF THE ECTOPIC INNER FOVEAL LAYERS IN EYES WITH IDIOPATHIC EPIRETINAL MEMBRANES: Surgical Results at 12 Months.

PURPOSE: To describe the functional and anatomical outcomes of pars plana vitrectomy with epiretinal membrane and internal limiting membrane peel in eyes with and without ectopic inner foveal layers (EIFLs). METHODS: In this retrospective multicenter study, patients diagnosed with idiopathic epiretinal membranes who underwent pars plana vitrectomy with epiretinal membrane and internal limiting membrane peel were enrolled, with a minimum follow-up of 12 months. Preoperative and postoperative spectral domain optical coherence tomography scans were qualitatively and quantitatively evaluated. The association of the EIFL and other spectral domain optical coherence tomography parameters with preoperative and postoperative best-corrected visual acuity (BCVA) was analyzed. RESULTS: One hundred eleven eyes of 107 patients were included. Preoperatively, the EIFLs were present in 56 of 111 eyes (50.4%). The presence of EIFL was significantly associated with lower preoperative and postoperative BCVA (P < 0.001). Ectopic inner foveal layer thickness was negatively correlated with preoperative BCVA (r = 0.58, P < 0.001). Postoperatively, the EIFL persisted in 51 of 56 eyes (91%) with Stage 3 and 4 epiretinal membranes. Ectopic inner foveal layer thickness decreased significantly after surgery (P < 0.001), but postoperative EIFL thinning had no direct effect on postoperative change in BCVA. At 12 months from surgery, EIFL thickness maintained a significant negative correlation with BCVA (r = 0.55, P < 0.001). CONCLUSION: The presence of EIFL should be considered a negative prognostic factor for postoperative anatomical and functional recovery.

Human L- and M-opsins restore M-cone function in a mouse model for human blue cone monochromacy.

Purpose: Blue cone monochromacy (BCM) is an X-linked congenital vision disorder characterized by complete loss or severely reduced L- and M-cone function. Patients with BCM display poor visual acuity, severely impaired color discrimination, myopia, nystagmus, and minimally detectable cone-mediated electroretinogram. Recent studies of patients with BCM with adaptive optics scanning laser ophthalmoscopy (AOSLO) showed that they have a disrupted cone mosaic with reduced numbers of cones in the fovea that is normally dominated by L- and M-cones. The remaining cones in the fovea have significantly shortened outer segments but retain sufficient structural integrity to serve as potential gene therapy targets. In this study, we tested whether exogenously expressed human L- and M-opsins can rescue M-cone function in an M-opsin knockout (Opn1mw-/- ) mouse model for BCM. Methods: Adeno-associated virus type 5 (AAV5) vectors expressing OPN1LW, OPN1MW, or C-terminal tagged OPN1LW-Myc, or OPN1MW-HA driven by a cone-specific promoter were injected subretinally into one eye of Opn1mw-/- mice, while the contralateral eye served as the uninjected control. Expression of cone pigments was determined with western blotting and their cellular localization identified with immunohistochemistry. M-cone function was analyzed with electroretinogram (ERG). Antibodies against cone phototransduction proteins were used to study cone outer segment (OS) morphology in untreated and treated Opn1mw-/- eyes. Results: We showed that cones in the dorsal retina of the Opn1mw-/- mouse do not form outer segments, resembling cones that lack outer segments in the human BCM fovea. We further showed that AAV5-mediated expression of either human M- or L-opsin individually or combined promotes regrowth of cone outer segments and rescues M-cone function in the treated Opn1mw-/- dorsal retina. Conclusions: Exogenously expressed human opsins can regenerate cone outer segments and rescue M-cone function in Opn1mw-/- mice, thus providing a proof-of-concept gene therapy in an animal model of BCM.

A clinical and molecular characterisation of CRB1-associated maculopathy.

To date, over 150 disease-associated variants in CRB1 have been described, resulting in a range of retinal disease phenotypes including Leber congenital amaurosis and retinitis pigmentosa. Despite this, no genotype-phenotype correlations are currently recognised. We performed a retrospective review of electronic patient records to identify patients with macular dystrophy due to bi-allelic variants in CRB1. In total, seven unrelated individuals were identified. The median age at presentation was 21 years, with a median acuity of 0.55 decimalised Snellen units (IQR = 0.43). The follow-up period ranged from 0 to 19 years (median = 2.0 years), with a median final decimalised Snellen acuity of 0.65 (IQR = 0.70). Fundoscopy revealed only a subtly altered foveal reflex, which evolved into a bull's-eye pattern of outer retinal atrophy. Optical coherence tomography identified structural changes-intraretinal cysts in the early stages of disease, and later outer retinal atrophy. Genetic testing revealed that one rare allele (c.498_506del, p.(Ile167_Gly169del)) was present in all patients, with one patient being homozygous for the variant and six being heterozygous. In trans with this, one variant recurred twice (p.(Cys896Ter)), while the four remaining alleles were each observed once (p.(Pro1381Thr), p.(Ser478ProfsTer24), p.(Cys195Phe) and p.(Arg764Cys)). These findings show that the rare CRB1 variant, c.498_506del, is strongly associated with localised retinal dysfunction. The clinical findings are much milder than those observed with bi-allelic, loss-of-function variants in CRB1, suggesting this in-frame deletion acts as a hypomorphic allele. This is the most prevalent disease-causing CRB1 variant identified in the non-Asian population to date.

OUTER RETINAL LAYER THICKNESS AS GOOD VISUAL PREDICTOR IN PATIENTS WITH DIABETIC MACULAR EDEMA.

PURPOSE: To evaluate the relationship between outer retinal layer (ORL) thickness in diabetic macular edema to visual acuity (VA). METHODS: Ninety-five eyes were included in this prospective nonrandomized case-control study. They divided into 30 cases of healthy normal subjects and 65 cases of nonproliferative diabetic retinopathy with diabetic macular edema. Complete ophthalmic examination and spectral domain-optical coherence tomography were done for all cases and analyzed to measure central foveal point thickness (CFT), ORL thickness at fovea, and subfoveal choroidal thickness. RESULTS: The ORL thickness was significantly thinner in diabetic macular edema group (85.3 µm) than controls (99.9 µm) (P = 0.002). There was higher significant correlation between ORL thickness and logMAR VA (r = -0.87, P < 0.001) than correlation between CFT and VA (r = 0.18, P = 0.16). The cutoff point of the relationship between ORL thickness and VA was 88 µm with moderate sensitivity (81%) and high specificity (88%), below which vision is affected. Outer retinal layer thickness is significantly related to subfoveal choroidal thickness but not CFT. CONCLUSION: This study revealed reduction in ORL thickness in diabetic macular edema. There is a higher and stronger correlation between ORL thickness and vision than that between CFT and vision.

INFLUENCE OF VITRECTOMY SURGERY ON THE INTEGRITY OF OUTER RETINAL LAYERS IN DIABETIC MACULAR EDEMA.

PURPOSE: To investigate the influence of pars plana vitrectomy (PPV) on the integrity of photoreceptor layers in eyes with diabetic macular edema (DME) by using parallelism (a parameter that comprehensively reflects photoreceptor-retinal pigment epithelium [RPE] complex alterations) in spectral-domain optical coherence tomography (SD-OCT) imaging. METHODS: A consecutive series of 64 eyes in 55 patients with diabetic macular edema who underwent pars plana vitrectomy were recruited into the study. Spectral-domain optical coherence tomography images were obtained preoperatively and 6 months after surgery. The morphologic features of the outer retinal layers were assessed quantitatively using parallelism and qualitatively by graders, including continuity of the external limiting membrane (ELM) line, continuity of the photoreceptor inner and outer segment (IS/OS) junction line, and the presence of hyperreflective foci in the outer retinal layers. The relationships between parallelism, visual acuity (VA), and photoreceptor layer status were evaluated. RESULTS: After surgery, foveal thickness significantly decreased (P < 0.0001) and visual acuity improved (P < 0.0001) from baseline level. Postoperative parallelism (0.632 ± 0.137) was significantly higher than preoperative parallelism (0.531 ± 0.172) (P < 0.0001). A number of eyes with hyperreflective foci reduced after surgery, while separate evaluation of the inner and outer segment junction and external limiting membrane lines did not show significant changes. Moreover, preoperative and postoperative parallelism values showed significant correlations with postoperative visual acuity and serum lipid levels. Foveal thickness and logMAR visual acuity did not show significant correlations with any blood test data. CONCLUSION: Pars plana vitrectomy might be effective for resolution of hyperreflective foci in outer retinal layers. Parallelism is a potential marker for localization of hyperreflective foci and useful as a predictive factor for postoperative visual acuity.

MULTIMODAL FUNDUS IMAGING OF OUTER RETINAL TUBULATIONS IN CHOROIDAL OSTEOMA PATIENTS.

PURPOSE: To evaluate the morphological findings of outer retinal tubulations (ORTs) shown on multimodal imaging modalities in patients with choroidal osteoma. METHODS: Nineteen eyes of 17 patients with choroidal osteoma underwent full clinical and imaging assessments. Color fundus photography, spectral-domain optical coherence tomography (OCT), and en face OCT were used to identify and detect the characteristics of ORT structures, including the shape, configuration, location, and distribution in the fundus. Optical coherence tomography angiography was implemented as an assist to differentiate tumor's feeder vessels from choroidal neovascularization. The correlations between age, gender, tumor features, best-corrected visual acuity at baseline, OCT characteristics, and the presence of ORTs were analyzed. RESULTS: Outer retinal tubulations were identified in five eyes (26.3%). All were located at the decalcified region of the tumor where the choroidal vessels, retinal pigment epithelium, and overlying outer retinal structures were considerably disrupted to varying degrees. With spectral-domain OCT, the ORTs appeared as one or multiple, round or ovoid, hyporeflective lumens with hyperreflective borders confined to the outer nuclear layer, sometimes with hyperreflective luminal content (four eyes, 80%). In one eye, ORTs were found at the focal choroidal excavation. On en face OCT, these tubulations exhibited different shapes, including a dendritic pattern in two eyes, a tube-like pattern in one eye, a circular pattern in one eye, and a hairpin pattern in one eye. Simultaneous OCT angiography imaging demonstrated that the area of choroidal neovascularization was underneath ORT in one eye and very close to ORT in two eyes. The ORTs of three eyes were above or adjacent to tumor's rich feeder vessels. Statistically, age (P = 0.007), greatest tumor linear dimension (P = 0.003), total tumor area (P = 0.002), decalcification area (P = 0.000), and the presence of intraretinal fluid (P = 0.01) and retinal pigment epithelium alterations (P = 0.038) within the foveola and central 1-mm region of patients with ORT were significantly different from those of patients without ORTs. CONCLUSION: The results of this study suggest that age, the greatest tumor linear dimension, total tumor area, decalcification area, and the presence of intraretinal fluid and retinal pigment epithelium alterations within the foveola and central 1-mm region might be risk factors for ORT formation. Spectral-domain OCT combined with en face OCT provides comprehensive imaging information for ORTs in choroidal osteoma.

CORRELATION BETWEEN INNER-RETINAL CHANGES AND OUTER-RETINAL DAMAGE IN PATIENTS WITH IDIOPATHIC EPIRETINAL MEMBRANE.

PURPOSE: To investigate correlations between the inner-retinal irregularity index and interdigitation zone (IZ) defects preidiopathic and postidiopathic epiretinal membrane (ERM) surgery. METHODS: The authors retrospectively assessed ophthalmic parameters in 89 eyes of 89 patients with ERM. They divided patients into the no-IZ defect (51, 57%) and IZ defect (38, 43%) groups. The IZ defect group was subdivided into recovered (22, 58%) and remaining IZ defect (16, 42%) subgroups, according to IZ recovery status at final examination. The inner-retinal irregularity index of each group was measured before and 1-, 3-, and 6-month postsurgery. RESULTS: Clinical characteristics were similar in both groups. The IZ defect group had a statistically significant higher inner-retinal irregularity index than the no-IZ defect group before (P = 0.023), but not after ERM surgery. The inner-retinal irregularity index of the recovered and remaining IZ defect subgroups was similar before surgery, but differed markedly 6 months after surgery (P = 0.048). Changes in the inner-retinal irregularity index quantitatively correlated with IZ defect size before and after ERM surgery (P < 0.001). CONCLUSION: The inner-retinal irregularity index differed significantly according to the IZ status and also correlated with the IZ defect before and after ERM surgery. The inner-retinal irregularity index may reflect the outer-retinal damage in ERM.

METAMORPHOPSIA AND OUTER RETINAL MORPHOLOGIC CHANGES AFTER SUCCESSFUL VITRECTOMY SURGERY FOR MACULA-OFF RHEGMATOGENOUS RETINAL DETACHMENT.

PURPOSE: To evaluate the correlation between metamorphopsia and outer retinal morphologic changes after successful vitrectomy for rhegmatogenous retinal detachment (RRD). METHODS: Forty eyes from 40 patients with macula-off (26 eyes) or macula-on (14 eyes) RRDs that underwent pars plana vitrectomy were included. Metamorphopsia was quantified with M-CHARTS. The relationship between the integrity of the outer retinal layers examined by spectral domain optical coherence tomography and metamorphopsia at 6 and 12 months postoperatively was evaluated. RESULTS: Metamorphopsia was significantly more frequent in eyes with macula-off RRD (88%) than in eyes with macula-on RRD (21%) at 6 months postoperatively (P < 0.001) and became significantly less frequent in macula-off RRD eyes from 6 months to 12 months (64%) postoperatively (P = 0.041). Horizontal metamorphopsia scores in eyes with continuous interdigitation zone and ellipsoid zone bands were significantly smaller than in eyes with a disrupted interdigitation zone band and a continuous ellipsoid zone band or in eyes with disrupted ellipsoid zone and interdigitation zone bands (P = 0.003 and P <0.001, respectively), which was consistent with the results of vertical metamorphopsia scores. CONCLUSION: Restoration of both the ellipsoid zone and interdigitation zone bands seems to be an important factor for the reduction of metamorphopsia after successful vitrectomy for macula-off RRD.

Outer Retinal Changes on Spectral-Domain Optical Coherence Tomography Pre- and Post-Silicone Oil Removal.

BACKGROUND AND OBJECTIVE: To evaluate outer retinal changes present on spectral-domain optical coherence tomography (SD-OCT) in eyes pre- and post-silicone oil (SiO) removal (SOR). PATIENTS AND METHODS: Retrospective case series of patients who underwent pars plana vitrectomy with SiO instillation and had SD-OCT completed pre- and post-SOR. SD-OCT parameters included presence of subretinal fluid, epiretinal membrane, ellipsoid zone disruption (EZD), external limiting membrane disruption, central subfield thickness (CST), and choroidal thickness. Visual acuities (VAs) and duration of SiO instillation were recorded. RESULTS: Thirty eyes of 30 patients were included. Mean Snellen VA pre- and post-SOR was 20/762 and 20/206, respectively (P < .001). Eyes with EZD under SiO had significantly longer duration of SiO tamponade (P = .029) along with worse VA post-SOR (P = .002). EZD was noted in 20 eyes with SiO and only 10 eyes post-SOR. Of these 10 eyes with resolution of EZD post-SOR, mean VA was significantly better (Snellen equivalent 20/133) compared to eyes with persistent EZD (Snellen equivalent 20/513; P = .01). CST and choroidal thickness decreased post-SOR (P = .117, P = .07). CONCLUSION: Outer retinal abnormalities on SD-OCT in SiO-filled eyes may improve in some patients following SOR. Some changes may be related to duration of SiO tamponade. EZD in SiO-filled eyes may portend a worse clinical outcome post-SOR despite surgical success. [Ophthalmic Surg Lasers Imaging Retina. 2017;48:978-982.].

Photoreceptor assessment using adaptive optics in resolved central serous chorioretinopathy / Avaliação dos fotorreceptores com adaptive optics na coriorretinopatia serosa central cicatrizada

ABSTRACT We present a case of a patient with resolved central serous chorioretinopathy (CSC) in the left eye with persistent mild visual alterations 4 years after the resolution of the disease. Left eye exam revealed a best corrected visual acuity of 20/25 and a slight change of macular pigmentation. Optical coherence tomography revealed only minor irregularities in the topography of retinal pigment epithelium and Bruch's membrane. Adaptive optics (AO) optics demonstrated lower density, spacing, and changes in the photoreceptor mosaic pattern in the left eye than in the right eye, suggesting that CSC may cause damage to cones after clinical recovery. We conclude that AO can provide additional information to assist in the treatment and follow-up of patients with CSC or other macular pathologies.

RESUMO Apresentamos o relato de caso de paciente com coriorretinopatia serosa central (CSC) cicatrizada em olho esquerdo e queixa de discreta alteração visual, mesmo após quatro anos da resolução do quadro. O exame do olho esquerdo apresenta melhor acuidade visual corrigida de 20/25 e discreta alteração de pigmentação macular. Tomografia de coerência óptica (OCT) apresentou apenas pequenas irregularidades em topografia de EPR e Bruch. Foi realizado exame com Adaptive Optics (AO), evidenciando valores inferiores de densidade, espaçamento e alterações no padrão de mosaico dos fotorreceptores em olho esquerdo quando comparado com olho direito, sugerindo que a CSC pode causar danos em cones, mesmo após uma recuperação considerada satisfatória. Concluímos que o AO é uma tecnologia que traz novas informações para auxiliar o tratamento e seguimento dos pacientes com CSC ou outras patologias maculares.

Correlation Between Mesopic Retinal Sensitivity and Optical Coherence Tomographic Metrics of the Outer Retina in Patients With Non-Atrophic Dry Age-Related Macular Degeneration.

BACKGROUND AND OBJECTIVE: To determine the correlation between mesopic retinal sensitivity and optical coherence tomographic metrics of the outer retina in patients with intermediate age-related macular degeneration (AMD). PATIENTS AND METHODS: Participants with nonatrophic dry AMD underwent mesopic MP-3 microperimetry (Nidek, Padova, Italy) and both Nidek and Cirrus (Carl Zeiss Meditec, Dublin, CA) spectral-domain optical coherence tomography (SD-OCT). The volume of the outer retinal layers was measured on the Nidek SD-OCT scans using the automatic segmentation algorithm of Navis-EX software. In addition, drusen area and volume within a 5-mm circle centered on the fovea were determined using the Cirrus Advanced RPE Analysis Tool. The mean retinal sensitivity at 8° and 10° of fixation (5-mm and 6-mm circles) was calculated for every eye. The correlation between retinal sensitivity and patient age, outer retinal layer volume, drusen area, and drusen volume was assessed. RESULTS: Thirty-seven eyes from 25 patients with non-atrophic dry AMD were included in the study. The mean age of the patients was 76 years ± 9 years. The mean sensitivity across the whole tested retinal area was 24.9 dB ± 2.4 dB, with a sensitivity of 25.1 dB ± 2.4 dB within the central 5-mm circle. Drusen area within the central 5-mm circle was 0.7 mm2 ± 0.89 mm2 with a drusen volume of 0.03 mm3 ± 0.04 mm3. Retinal pigment epithelium and photoreceptor outer segment (RPE + OS) volume was 1.96 mm3 ± 0.1 mm3, and outer nuclear layer (ONL) volume was 1.91 mm3 ± 0.17 mm3. There was a significant correlation between RPE + OS volume and retinal sensitivity, as well as between patients' age and retinal sensitivity. There was no significant correlation between drusen area or volume and retinal sensitivity, nor between ONL volume and retinal sensitivity. CONCLUSION: In eyes with nonatrophic AMD, retinal sensitivity is correlated with the RPE + OS volume, but not the ONL volume or the area or volume of drusen. [Ophthalmic Surg Lasers Imaging Retina. 2017;48:312-318.].