Photoreceptor Outer Segment Length Research Articles

Visual pigment concentration and photoreceptor outer segment length in the human retina.

The Beer-Lambert law suggests that visual pigment optical density (OD) should be linearly related to the length of photoreceptor outer segments (POSs). Mammalian studies indicate that visual pigment concentration increases with POS length, but the nature of this relationship may vary due to factors such as visual pigment packing density or retinal eccentricity, and may not necessarily be linearly related. The purpose of this study was to establish the relationship between OD and POS length in humans. Spectral domain optical coherence tomography (OCT) was used to image POS, and imaging retinal densitometry (IRD) was used to measure OD at corresponding locations in 19 healthy participants (age range 25-82 years). POS length and OD measurements were extracted from OCT and IRD images at 23 discrete locations spanning the central 9° of the retina. The averaged data from all participants were fitted with models based on the Beer-Lambert law to establish the relationship between OD and POS length. Visual pigment OD increased monotonically with POS length, but the relationship was non-linear, and a straight-line fit, based on a simple interpretation of the Beer-Lambert law, provided a poor description. A model allowing for different rod and cone visual pigment concentrations provided a superior fit. Specifically, the data were well described by a model where the molar concentration of visual pigment in cones and rods were 3.8 × 10-3 mol/L and 1.8 × 10-3mol/L, respectively. In accordance with the Beer-Lambert law, the results indicate that OD increases monotonically with POS length in humans, but the precise relationship is dependent on photoreceptor type. These results suggest that visual pigment concentration in rods is only about 48% of that found in cones. This may be due to the ubiquitous nature of artificial light that works to reduce the concentration of rhodopsin in rod photoreceptors.

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.

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). 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. 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. 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.

Genotype-Phenotype Associations in an X-Linked Retinoschisis Patient Cohort: The Molecular Dynamic Insight and a Promising SD-OCT Indicator.

This study investigated a three-dimensional indicator in spectral-domain optical coherence tomography (SD-OCT) and established phenotype-genotype correlation in X-linked retinoschisis (XLRS). Thirty-seven patients with XLRS underwent comprehensive ophthalmic examinations, including visual acuity (VA), fundus examination, electroretinogram (ERG), and SD-OCT. SD-OCT parameters of central foveal thickness (CFT), cyst cavity volume (CCV), and photoreceptor outer segment length were assessed. CCV was defined as the sum of the areas of cyst cavities in uential B-scans, measured automatically by self-developed software (OCT-CCSEG). Structural changes of the protein associated with missense variants were quantified by molecular dynamics (MD). The correlation between genotype and phenotype was analyzed. Twenty-seven different RS1 variants were identified, including a novel variant c.336_337insT(p.L113Sfs*8). The average age of onset was 14.76 ± 15.75years, and the mean VA was 0.84 ± 0.43 logMAR. The mean CCV was 1.69 ± 1.87mm3, correlating significantly with CFT (R = 0.66; P < 0.01). In the genotype-phenotype analysis of missense variants, CCV significantly correlated with the structural effect on the protein of mutational changes referred to as wild type, including root-mean-square deviation (R = 0.34; P = 0.04), solvent accessible surface area (R = 0.38; P = 0.02), and surface hydrophobic area (R = 0.37; P = 0.03). The amplitude of scotopic 3.0 ERG a-waves and b-waves significantly correlated with the percentage change of the β-strand in the secondary structure (a-wave: R = -0.58, P < 0.01; b-wave: R = -0.53, P < 0.01). CCV is a promising indicator to quantify the structural disorganization of XLRS retina. The OCT-CCSEG software calculated CCV automatically, potentially facilitating prognosis assessment and development of personalized treatment. Moreover, MD-involved genotype-phenotype analysis suggests an association between protein structural alterations and XLRS severity measured by CCV and ERG.

The role of optical coherence tomography biomarkers in predicting the outcome of epiretinal membrane removal surgery

Epiretinal membrane (ERM) is a common condition that can cause visual impairment. ERM removal surgery is an effective treatment option, but predicting postoperative visual outcomes is challenging. Imaging modalities, particularly optical coherence tomography (OCT), have emerged as valuable tools for preoperative evaluation and predicting surgical outcomes. This presentation focuses on the role of preoperative OCT biomarkers in estimating postoperative vision improvement after ERM removal surgery. Such biomarkers include the disorganization of retinal inner layers (DRIL), the presence of ectopic inner foveal layer (EIFL), the cotton ball sign, the cone outer segment tips (COST) line, the photoreceptor outer segment (PROS) length, the inner retina irregularity index, and the presence of posterior vitreous detachment (PVD).DRIL refers to the abnormal appearance of the inner retinal layers on OCT, and has been found to be associated with poorer postoperative visual outcomes in ERM removal surgery. Significant EIFL has also been associated with poorer visual outcomes after surgery. The cotton ball sign, which appears as a hyper‐reflective area in the inner nuclear layer, has been found to be associated with increased difficulty in ERM removal and poorer visual outcomes. These biomarkers suggest that a greater degree of retinal disorganization and irregularity may lead to more challenging surgeries and poorer visual outcomes.In contrast, the presence of intact COST line and normal PROS length have been associated with better visual function. PVD, which represents separation of the vitreous from the retina, has been shown to be associated with less surgical trauma and better postoperative outcomes. The inner retina irregularity index, which measures the extent of disorganization of the inner retinal layers, has also been found to correlate with the changes in metamorphopsia and quality of vision after surgery.These biomarkers have the potential to improve the accuracy of preoperative evaluation and prediction of surgical outcomes in ERM removal surgery. By identifying patients with a greater degree of retinal disorganization and irregularity, we can anticipate more challenging surgeries and poorer visual outcomes. Conversely, patients with minimal COST line defects, normal PROS length and full PVD may have better postoperative visual outcomes.In summary, preoperative OCT findings can help predict postoperative visual outcomes in ERM removal surgery. The use of imaging modalities and specific biomarkers can provide useful insight in management decisions, case selection, and timing of surgery.

Diabetic choriocapillaris flow deficits affect the outer retina and are related to hemoglobin A1c and systolic blood pressure levels

Patient systemic and ocular data based on optical coherence tomography (OCT) and OCT angiography images were analyzed (n = 45; control and diabetic eyes with or without diabetic retinopathy [DR]; mean age, 49.6 ± 8.1 years). All participants had best-corrected visual acuity < 0.05 in logMAR. The choriocapillaris flow area (CCFA) ratio was lower and the coefficient of variation (CV) of CCFA ratio was higher in diabetic eyes with or without DR than in control eyes. CCFA ratio of DR eyes was lower than that of diabetic eyes without DR. Superficial retinal vessel length density (VLD) was reduced only in DR eyes. CCFA ratio correlated with retinal VLD, photoreceptor outer segment (PROS) length, and retinal pigment epithelium (RPE) volume in the study population; mean PROS decreased in diabetic eyes with or without DR, and RPE volume increased in DR eyes. CCFA ratio < 65.9% and CV of CCFA ratio ≥ 0.140 were more frequently found in diabetic eyes (odds ratio [OR], 13.333; P = 0.001), and related to HbA1c ≥ 7.0% (OR, 4.992; 95% confidence interval [CI] 1.164–21.412; P = 0.030) or systolic blood pressure ≥ 135 mmHg (OR, 5.572; 95% CI 1.156–26.863; P = 0.032). These findings could help understand diabetic pathogenesis in the choriocapillaris and outer retina, and remind clinicians to manage both diabetes and hypertension.

Spatially-dependent model for rods and cones in the retina

We develop a mathematical model for photoreceptors in the retina. We focus on rod and cone outer segment dynamics and interactions with a nutrient source associated with the retinal pigment epithelium cells. Rod and cone densities (number per unit area of retinal surface) are known to have significant spatial dependence in the retina with cones located primarily near the fovea and the rods located primarily away from the fovea. Our model accounts for this spatial dependence of the rod and cone photoreceptor density as well as for the possibility of nutrient diffusion. We present equilibrium and dynamic solutions, discuss their relation to existing models, and estimate model parameters through comparisons with available experimental measurements of both spatial and temporal photoreceptor characteristics. Our model compares well with existing data on spatially-dependent regrowth of photoreceptor outer segments in the macular region of Rhesus Monkeys. Our predictions are also consistent with existing data on the spatial dependence of photoreceptor outer segment length near the fovea in healthy human subjects. We focus primarily on the healthy eye but our model could be the basis for future efforts designed to explore various retinal pathologies, eye-related injuries, and treatments of these conditions.

Diurnal functional and anatomical changes in X-linked retinoschisis

BackgroundTo investigate the changes in macular cystic schisis (MCS) and sensitivity during the day in X-linked retinoschisis (XLRS) patients.MethodsTreatment-naïve patients with genetically verified XLRS underwent best-correlated visual acuity (BCVA) testing with ETDRS charts, spectral domain optical coherence tomography, and microperimetry (MP) twice a day, at 9 a.m. and 4 p.m., to measure changes in central retinal thickness (CRT), macular volume (MV), average threshold (AT), and fixation stability parameters (P1 and P2).ResultsAt baseline, the BCVA of the 14 eyes of 8 patients amounted 0.73 (± 0.23) LogMAR. Between timepoints, the BCVA increased in 3.21 letters (p = .021), the AV improved in 1.84 dB (p = .03, 9.73%), the CRT decreased in 24.43 µm (p = .007, − 4.05%), and the MV dropped in 0.27 µm3 (p = .016, − 2.68%). P1 and P2 did not variate. The collapse of the MCS led to the reduction of macula thickness. CRT at baseline correlated with the decrease of CRT (Spearman’s ρ: − 0.83 [p = .001]). Age and change of BCVA, CRT, and AV did not correlate among one another. Eyes with disrupted ellipsoid zone showed a more prominent change in CRT (p = .050). Photoreceptor outer segment length and integrity of the external limiting membrane and cone outer segment tips were not associated with BCVA, AT, or CRT variation.ConclusionEyes of treatment-naïve XLRS patients show diurnal macular thickness and function changes. Eyes with pronounced macular thickness show a greater reduction of the MCS. These results should be taken into consideration in upcoming clinical trials in XLRS.Trial registration numberInstitutional Review Board of the Hamburg Medical Chamber (Ethik-Kommission der Ärztekammer Hamburg): 2020–10,328.

Evaluation of the optical coherence tomography findings of patients with idiopathic epiretinal membrane.

This study aimed to determine the relationship between basal visual acuity (VA) and basal optical coherence tomography (OCT) parameters of patients with idiopathic epiretinal membrane (iERM). The study included 200 eyes of 200 patients with iERM. In the evaluation of basal VAs, logMAR 0.3 (0.5 on Snellen chart) was accepted as the limit, and the patients were divided into two groups as Group 1 with VA values below logMAR 0.3 and Group 2 with those above logMAR 0.3. Using OCT, the ellipsoid zone (EZ), interdigitation zone (IZ), external limiting membrane (ELM) integrity, peaked appearance of EZ in the fovea, disorganization of the inner retinal layers (DRIL), central foveal thickness (CFT), maximum retinal thickness (MRT), total photoreceptor length (TPL), photoreceptor outer segment length (PROSL), photoreceptor deformity index (PDI), and inner retinal layer irregularity index (IRLII) were evaluated and compared between the groups. There were an equal number of patients in Group 1 and Group 2. The preservation of ELM, EZ, and IZ integrity and the peaked appearance of EZ in the fovea were observed at higher rates in Group 1, whereas the rate of DRIL was higher in Group 2 (p<0.05 for all). In the multiple regression analysis performed to evaluate categorical OCT parameters, only the presence of DRIL was found to be significantly associated with VA (p<0.003). CFT*, MRT*, and IRLII** were significantly lower in Group 1 (*p<0.001, **p=0.001). TPU, PROSL, and FDI were similar between the two groups (p>0.05 for all). According to the multiple regression analysis, only the presence of DRIL was correlated with lower VA values. Among the OCT parameters, an increase in CFT and MRT, as well as the IRLII value moving away from 1 were related to lower VA values.

Chromatin remodeler Chd7 regulates photoreceptor development and outer segment length

Mutations in the chromatin remodeling factor CHD7 are the predominant cause of CHARGE syndrome, a congenital disorder that frequently includes ocular coloboma. Although CHD7 is known to be required for proper ocular morphogenesis, its role in retinal development has not been thoroughly investigated. Given that individuals with CHARGE syndrome can experience visual impairment even in the absence of coloboma, a better understanding of CHD7 function in the retina is needed. In this study, we characterized the expression pattern of Chd7 in the developing zebrafish and mouse retina and documented ocular and retinal phenotypes in Chd7 loss-of-function mutants. Zebrafish Chd7 was expressed throughout the retinal neuroepithelium when retinal progenitor cells were actively proliferating, and later in subsets of newly post-mitotic retinal cells. At stages of retinal development when most retinal cell types had terminally differentiated, Chd7 expression remained strong in the ganglion cell layer and in some cells in the inner nuclear layer. Intriguingly, strong expression of Chd7 was also observed in the outer nuclear layer where it was co-expressed with markers of post-mitotic cone and rod photoreceptors. Expression of mouse CHD7 displayed a similar pattern, including expression in the ganglion cells, subsets of inner nuclear layer cells, and in the distal outer nuclear layer as late as P15. Two different mutant chd7 zebrafish lines were characterized for ocular and retinal defects. These mutants displayed microphthalmia, reduced numbers of cone photoreceptors, and truncated rod and cone photoreceptor outer segments. Reduced cone photoreceptor number and abnormal outer segments were also observed in heterozygous Chd7 mutant mice. Taken together, our results in zebrafish and mouse reveal a conserved, previously undescribed role for Chd7 in retinal development and photoreceptor outer segment morphogenesis. Moreover, our work suggests an avenue of future investigation into the pathogenesis of visual system defects in CHARGE syndrome.

MACULAR MICROVASCULATURE IN X-LINKED RETINOSCHISIS: Optical Coherence Tomography and Optical Coherence Tomography Angiography Study.

The study aimed to evaluate the macular microvasculature of X-linked retinoschisis (XLRS) and identify correlations between vascular changes, structural changes, and functional outcome. Genetically confirmed XLRS patients and heathy control subjects underwent complete ophthalmic examination, dilated funduscopic examination, optical coherence tomography, and optical coherence tomography angiography. Schisis distribution, outer plexiform layer discontinuation, photoreceptor layer thickness, and photoreceptor outer segment length were reviewed using optical coherence tomography. Vascular flow density and foveal thickness at foveal and parafoveal area were measured using optical coherence tomography angiography. A total of 17 eyes of 9 XLRS patients and 22 eyes of 11 control subjects were examined from July 2018 to August 2020. Flow density in the deep capillary plexus at foveal and parafoveal area decreased in XLRS patients compared with control subjects (P = 0.014 and 0.001, respectively), whereas foveal avascular zone area and perimeter remarkably increased (P = 0.015 and 0.001, respectively). Although outer and total retinal layers were significantly thicker in XLRS, inner retinal layer was thinner with reduced photoreceptor layer thickness and shortened photoreceptor outer segment length (P < 0.001 and P < 0.001, respectively). Foveal flow loss in deep capillary plexus, foveal avascular zone enlargement, thinner inner retina and photoreceptor layer thickness, and shortened photoreceptor outer segment length correlated with best-corrected visual acuity. X-linked retinoschisis eyes exhibit decreased flow density in the deep capillary plexus and variable foveal avascular zone with enlarged perimeter. Structural deterioration of the photoreceptor best reflects the degenerative changes, whereas microvascular alteration shows considerable correlation with functional outcome in XLRS.

Preoperative ocular coherence tomographic prognosticators of visual acuity after idiopathic epiretinal membrane surgery.

To provide a current review of the evidence for the utility of preoperative ocular coherence tomography (OCT) parameters in prognosticating postoperative visual acuity and visual improvement after idiopathic epiretinal membrane surgery. To determine which OCT bio-markers are most useful in this regard and where future studies may apply more emphasis. An extensive search of the PubMed database was performed for studies investigating this relationship. Key search terms included: idiopathic, epiretinal membrane, surgery, peel, vitrectomy, vision, outcomes, visual acuity, ocular coherence tomography, central foveal thickness, foveal contour, foveal morphology, ectopic inner foveal layers, inner retinal layers, inner retinal irregularity index, outer retinal layers, ellipsoid zone, interdigitation zone, photoreceptor outer segment length, central bouquet abnormality, staging, choroidoscleral irregularity, ganglion cell and nerve fibre layers, inner and outer plexiform layers, inner and outer nuclear layers. Forty-nine peer-reviewed articles were included in this review. These consisted of 28 retrospective studies [1-3,13,16-18,20,23-29,32-36,38,40,42-47], 17 prospective studies[6-12,14,19,21,22,30,31,37,41,48,49], 2 reviews [4,39] and 2 systematic reviews [5,15]. The weight of literary evidence seems to support photoreceptor integrity as the most consistent OCT marker of better postoperative visual acuity. This includes analysis of ellipsoid and interdigitation zones as well as photoreceptor outer segment length. However, the newer OCT staging system proposed by Govetto et al. (2017) fulfils a need for a clinically useful and evidence-based OCT classification. It may be the way forward in prognosticating ERM surgical outcomes by preoperative stratification. There is insufficient evidence to suggest the other discussed parameters in this review as useful prognosticators of postoperative visual acuity.

X-Linked Retinoschisis: Novel Clinical Observations and Genetic Spectrum in 340 Patients

To describe the natural course, phenotype, and genotype of patients with X-linked retinoschisis (XLRS). Retrospective cohort study. Three hundred forty patients with XLRS from 178 presumably unrelated families. This multicenter, retrospective cohort study reviewed medical records of patients with XLRS for medical history, symptoms, visual acuity (VA), ophthalmoscopy, full-field electroretinography, and retinal imaging (fundus photography, spectral-domain [SD] OCT, fundus autofluorescence). Age at onset, age at diagnosis, severity of visual impairment, annual visual decline, and electroretinography and imaging findings. Three hundred forty patients were included with a mean follow-up time of 13.2 years (range, 0.1-50.1 years). The median ages to reach mild visual impairment and low vision were 12 and 25 years, respectively. Severe visual impairment and blindness were observed predominantly in patients older than 40 years, with a predicted prevalence of 35% and 25%, respectively, at 60 years of age. The VA increased slightly during the first 2 decades of life and subsequently transitioned into an average annual decline of 0.44% (P < 0.001). No significant difference was found in decline of VA between variants that were predicted to be severe and mild (P= 0.239). The integrity of the ellipsoid zone (EZ) as well as the photoreceptor outer segment (PROS) length in the fovea on SD OCT correlated significantly with VA (Spearman's ρ= -0.759 [P < 0.001] and -0.592 [P = 0.012], respectively). Fifty-three different RS1 variants were found. The most common variants were the founder variant c.214G→A (p.(Glu72Lys)) (101 patients [38.7%]) and a deletion of exon 3 (38 patients [14.6%]). Large variabilities in phenotype and natural course of XLRS were seen in this study. In most patients, XLRS showed a slow deterioration starting in the second decade of life, suggesting an optimal window of opportunity for treatment within the first 3 decades of life. The integrity of EZ as well as the PROS length on SD OCT may be important in choosing optimal candidates for treatment and as potential structural end points in future therapeutic studies. No clear genotype-phenotype correlation was found.

Geometrical scaling of the developing eye and photoreceptors and a possible relation to emmetropization and myopia

In this study the role of vergence in relation to age-dependent scaling of eye and photoreceptor parameters is studied. The underlying hypothesis is that the size and packing of outer segments is matched to the pupil size outdoors in photopic conditions. Vergence is analysed in relation to the angular spectrum of waves being incident using age-dependent data from the literature for the actual geometry and density of photoreceptor cones and rods. This approach is used to derive simple relations for the angular confinement of light along outer segments. Only with a small photopic pupil can leakage and crosstalk for both central and peripheral photoreceptors be entirely ruled out due to the finite length of the outer segments. A limiting 3 mm pupil size is found for children in the school age. Larger pupils will increase the likelihood of leakage and crosstalk that may therefore impact on emmetropization. This study has introduced a new paradigm in myopia research by considering vergence across the 3-D retina as being matched to the angular spectrum of waves being incident from the eye pupil. Emmetropization suggests a delicate balance between photoreceptor outer segment length and density in relation to pupil size. Only when balanced will leakage and crosstalk between adjacent outer segments be effectively suppressed thereby ensuring the highest possible light capture efficiency by visual pigments in the outer segments whether an image is formed on the retina or not.

The Relationship Between Visual Sensitivity and Eccentricity, Cone Density and Outer Segment Length in the Human Foveola.

PurposeThe cellular topography of the human foveola, the central 1° diameter of the fovea, is strikingly non-uniform, with a steep increase of cone photoreceptor density and outer segment (OS) length toward its center. Here, we assessed to what extent the specific cellular organization of the foveola of an individual is reflected in visual sensitivity and if sensitivity peaks at the preferred retinal locus of fixation (PRL).MethodsIncrement sensitivity to small-spot, cone-targeted visual stimuli (1 × 1 arcmin, 543-nm light) was recorded psychophysically in four human participants at 17 locations concentric within a 0.2° diameter on and around the PRL with adaptive optics scanning laser ophthalmoscopy-based microstimulation. Sensitivity test spots were aligned with cell-resolved maps of cone density and cone OS length.ResultsPeak sensitivity was at neither the PRL nor the topographical center of the cone mosaic. Within the central 0.1° diameter, a plateau-like sensitivity profile was observed. Cone density and maximal OS length differed significantly across participants, correlating with their peak sensitivity. Based on these results, biophysical simulation allowed to develop a model of visual sensitivity in the foveola, with distance from the PRL (eccentricity), cone density, and OS length as parameters.ConclusionsSmall-spot sensitivity thresholds in healthy retinas will help to establish the range of normal foveolar function in cell-targeted vision testing. Because of the high reproducibility in replicate testing, threshold variability not explained by our model is assumed to be caused by individual cone and bipolar cell weighting at the specific target locations.

Functional optoretinography: concurrent OCT monitoring of intrinsic signal amplitude and phase dynamics in human photoreceptors.

Intrinsic optical signal (IOS) imaging promises a noninvasive method for objective assessment of retinal function. This study demonstrates concurrent optical coherence tomography (OCT) of amplitude-IOS and phase-IOS changes in human photoreceptors. A new procedure for differential-phase-mapping (DPM) is validated to enable depth-resolved phase-IOS imaging. Dynamic OCT revealed rapid amplitude-IOS and phase-IOS changes, which occur almost right away after the stimulus onset. These IOS changes were predominantly observed within the photoreceptor outer segment (OS), particularly two boundaries connecting to the inner segment and retinal pigment epithelium. The comparative analysis supports that both amplitude-IOS and phase-IOS attribute to transient OS morphological change associated with phototransduction activation in retinal photoreceptors. A simulation modeling is proposed to discuss the relationship between the photoreceptor OS length and phase-IOS changes.

Optical coherence tomography biomarkers for visual acuity in patients with idiopathic epiretinal membrane.

To investigate the correlation between outer and inner retina optical coherence tomography (OCT) biomarkers and visual acuity in patients with idiopathic epiretinal membrane (iERM) and identify which of them may be predictive of visual function. A retrospective cross-sectional single-center study was conducted that included patients diagnosed with iERM. Spectral domain OCT images were obtained and assessed qualitatively and quantitatively. The association of OCT parameters with best corrected visual acuity was analyzed. Charts of 97 eyes of 97 patients were reviewed. Central foveal thickness, maximal retinal thickness (MRT), photoreceptor outer segment length, outer foveal thickness, ganglion cell-inner plexiform layer complex thickening, inner retinal thickness and inner retinal layer irregularity index were among the major outcome measures. OCT scans were also assessed for the presence of cotton ball sign, ellipsoid zone disruption, ectopic inner foveal layer, disorganization of retinal inner layers (DRIL), intraretinal fluid, subretinal fluid (SRF) and epimacular membrane rip. Univariate analysis showed statistically significant association between all the aforementioned parameters with worse vision, except for cotton ball sign and SRF. Multivariate analysis found that MRT and severe DRIL were strongly correlated with worse vision (p < 0.001). MRT and severe DRIL should be considered as negative prognostic factors for visual acuity.

Macular Pigment Optical Density and Photoreceptor Outer Segment Length as Predisease Biomarkers for Age-Related Macular Degeneration.

To explore predisease biomarkers, which may help screen for the risk of age-related macular degeneration (AMD) at very early stages, macular pigment optical density (MPOD) and photoreceptor outer segment (PROS) length were analyzed. Thirty late AMD fellow eyes, which are at high risk and represent the predisease condition of AMD, were evaluated and compared with 30 age-matched control eyes without retinal diseases; there was no early AMD involvement in the AMD fellow eyes. MPOD was measured using MPS2® (M.E. Technica Co. Ltd., Tokyo, Japan), and PROS length was measured based on optical coherence tomography images. MPOD levels and PROS length in the AMD fellow eyes were significantly lower and shorter, respectively, than in control eyes. MPOD and PROS length were positively correlated in control eyes (R = 0.386; p = 0.035) but not in AMD fellow eyes. Twenty (67%) AMD fellow eyes met the criteria of MPOD < 0.65 and/or PROS length < 35 μm, while only five (17%) control eyes did. After adjusting for age and sex, AMD fellow eyes more frequently satisfied the definition (p < 0.001; 95% confidence interval, 3.50–60.4; odds ratio, 14.6). The combination of MPOD and PROS length may be a useful biomarker for screening predisease AMD patients, although further studies are required in this regard.

ELONGATED PHOTORECEPTOR OUTER SEGMENT LENGTH AND PROGNOSIS OF CHRONIC CENTRAL SEROUS CHORIORETINOPATHY.

To evaluate the effect of elongated photoreceptor outer segment length on the visual prognosis of patients with chronic central serous chorioretinopathy after treatment using half-dose and half-fluence photodynamic therapy (reduced PDT). The study included 36 eyes of 36 patients with chronic central serous chorioretinopathy who underwent reduced PDT and were followed up for at least 1 year. Spectral domain optical coherence tomography measurement was conducted at baseline and 12 months after reduced PDT. Thereafter, the association between the best-corrected visual acuity (BCVA) at 12 months after reduced PDT and 7 baseline variables (age, symptom duration, BCVA, outer nuclear layer thickness, elongated photoreceptor outer segment length, height of subretinal detachment, and subfoveal choroidal thickness) was evaluated. Multivariate analyses using the model selection with the corrected Akaike Information Criterion index were performed. The optimal model for BCVA at 12 months only included baseline BCVA (coefficient = 0.90, P < 0.0001) and baseline elongated photoreceptor outer segment length (coefficient = -0.0016, P = 0.034), but not outer nuclear layer thickness. Elongated photoreceptor outer segment length was significantly associated with BCVA prognosis in patients with chronic central serous chorioretinopathy after reduced PDT and can be useful for predicting residual photoreceptor function during the active phase of chronic central serous chorioretinopathy.

Early Cone Photoreceptor Outer Segment Length Shortening in RPGR X-Linked Retinitis Pigmentosa

Introduction: Introduction of retinal gene therapy requires established outcome measures along with thorough understanding of the pathophysiology. Evidence of early, thinned outer segments in RPGR X-linked retinitis pigmentosa could help understand how the level of cone photoreceptor involvement translates to visual potential. Objective: Analysis of foveal photoreceptor outer segment length in a young cohort of RPGR patients to help clarify the reason for absent maximal visual acuity seen. Methods: Case-control study of RPGR patients. Quantitative measurement of photoreceptor outer segment by OCT. Results: Eighteen male RPGR patients and 30 normal subjects were included. Outer segment thickness differed significantly between the RPGR and normal eyes (p < 0.0005). Mean outer segment values were 35.6 ± 2.3 µm and 35.4 ± 2.6 µm for RPGR right and left eyes, respectively. In normal eyes, the mean outer segment thickness was 61.4 ± 0.7 µm for right eyes and 62.4 ± 0.7 µm for left eyes. Conclusions: Patients with RPGR X-linked retinitis pigmentosa show thinning of the foveal photoreceptor outer segment thickness early in the disease course, which could be an explanation for the lower maximum visual acuity seen. These findings must be taken into consideration when assessing efficacy outcome measures in retinal gene therapy trials.

Retinal structural changes in patients receiving tamoxifen therapy by spectral-domain optical coherence tomography

Purpose: To evaluate choroidal thickness, ganglion cell complex (GCC) and photoreceptor outer segment (PROS) length were measured in patients with breast cancer undergoing tamoxifen therapy, using spectral-domain optical coherence tomography (SD-OCT); results were compared with those for normal eyes.Materials and methods: Forty-four patients with breast cancer, undergoing tamoxifen therapy, and 41 healthy controls were included in this prospective, comparative study. All participants underwent a complete ophthalmologic evaluation and SD-OCT. Subfoveal, nasal (nasal distance to fovea 500, 1000, 1500 μm), and temporal (temporal distance to fovea 500, 1000, 1500 μm) choroidal thickness measurements were performed using the enhanced depth imaging mode of SD-OCT. Using an Early Treatment Diagnostic Retinopathy Study (ETDRS) circle at the macular level, the automated retinal segmentation software was applied to determine the thickness of the GCC. PROS length was determined manually, as the distance from the inner surface of the ellipsoid zone to the inner surface of retina pigment epithelium.Results: The mean choroidal thickness was statistically greater in the tamoxifen group than controls in all quadrants (p < 0.001 for all quadrants). Of all tamoxifen users (44 eyes of 44 patients), 33 eyes (75%) had uncomplicated pachychoroid (UCP). Pachychoroid pigment epitheliopathy (PPE) was detected in five tamoxifen-group patients (11.3%). Patients with PPE in one eye had UCP in the fellow eye. Central serous chorioretinopathy findings were observed in one patient. Tamoxifen users had statistically lower GCC thickness in all inner rings of the ETDRS inlay and in the nasal outer ring only (p = 0.027, 0.002, 0.002, 0.001, and 0.030, respectively). No statistically significant difference in mean subfoveal PROS length was found between the groups.Conclusions: SD-OCT provides valuable information for identifying structural changes and evaluating ocular findings in patients receiving tamoxifen therapy. Increased choroidal thickness, PPE and thinning GCC were detected in tamoxifen users. These OCT findings may be an early indicator of retinal toxicity for patients undergoing tamoxifen therapy in the follow-up period.