Retinal Sensitivity Research Articles

Multiwavelength photobiomodulation in atrophic age-related macular degeneration.

To evaluate photobiomodulation (PBM) safety and efficacy in patient with atrophic AMD and to explore tissue effects using Spectrally Resolved Autofluorescence (SrAF) to identify a potential biomarker indicative of mitochondrial activity, the primary PBM target. This retrospective, non-comparative case series involved six eyes of five patients with atrophic AMD, conducted at the Medical Retina and Imaging Unit, IRCCS San Raffaele Hospital in Milan, Italy. At baseline and follow-ups (after one and three months) a complete ophthalmological assessment and multimodal imaging, including spectrally resolved autofluorescence (SrAF), were performed. PBM treatment (Valeda Light Delivery System - LumiThera) was administered in nine sessions over three weeks. The SrAF images were analyzed to evaluate the effect of the treatment. Six eyes of five patients with atrophic AMD received PBM at baseline. Best corrected visual acuity (BCVA), mean central macular thickness (CMT), mean retinal sensitivity on microperimetry and the atrophic area have remained stable. No eyes developed foveal atrophy after the treatment. The image analysis in SrAF showed an increase in the highlighted area of 4.89% after one month and 17.11% after three months. No adverse systemic or local side effects were reported. PBM is a safe treatment for the human retina. The evaluation of the retinal area within the green light spectrum (575 nm) in SrAF is a potential indirect biomarker of mitochondrial activity and could be used to assess treatment efficacy in clinical studies.

The relationship between spectral signals and retinal sensitivity in dendrobatid frogs.

Research on visually driven behavior in anurans has often focused on Dendrobatoidea, a clade with extensive variation in skin reflectance, which is perceived to range from cryptic to conspicuous coloration. Because these skin patterns are important in intraspecific and interspecific communication, we hypothesized that the visual spectral sensitivity of dendrobatids should vary with conspecific skin spectrum. We predicted that the physiological response of frog retinas would be tuned to portions of the visible light spectrum that match their body reflectance. Using wavelength-specific electroretinograms (ERGs; from 350-650 nm), spectrometer measurements, and color-calibrated photography of the skin, we compared retinal sensitivity and reflectance of two cryptic species (Allobates talamancae and Silverstoneia flotator), two intermediate species (Colostethus panamansis and Phyllobates lugubris), and two conspicuous aposematic species (Dendrobates tinctorius and Oophaga pumilio). Consistent with the matched filter hypothesis, the retinae of cryptic and intermediate species were sensitive across the spectrum, without evidence of spectral tuning to specific wavelengths, yielding low-threshold broadband sensitivity. In contrast, spectral tuning was found to be different between morphologically distinct populations of O. pumilio, where frogs exhibited retinal sensitivity better matching their morph's reflectance. This sensory specialization is particularly interesting given the rapid phenotypic divergence exhibited by this species and their behavioral preference for sympatric skin reflectances. Overall, this study suggests that retinal sensitivity is coevolving with reflective strategy and spectral reflectance in dendrobatids.

THE RELATIONSHIP BETWEEN RETINAL PERFUSION AND FUNCTIONAL RECOVERING OF FOVEA IN DIFFERENT TYPES OF SURGICAL CLOSURE OF FULL-THICKNESS MACULAR HOLES

Rationale: The effect of retinal perfusion on functional recovery of the fovea, as well as the value of quantitative perfusion parameters as predictors of functional outcome in the surgical treatment of full-thickness macular holes (FTMH) remains poorly understood.Objective: To study the relationship between changes in retinal perfusion and functional parameters of the fovea in the postoperative period at 1 and 2 types of FTMH closure.Methods: A prospective study including 93 patients (93 eyes) with idiopathic FTMH stage 2-4 according to D. Gass after surgical treatment. In subgroups with type 1 and type 2 of FTMH closure, changes in the foveal avascular zone (FAZ) area and vessel density in the superficial and deep capillary plexuses (SCP and DCP) in the fovea, changes in BCVA, retinal sensitivity (RS) at the fixation point, and P1 amplitude in the fovea were studied. Studies were performed preoperatively, 1 and 6 months after surgery. A significant correlation was found between the changes in BCVA, RS at the fixation point, P1 amplitude in the fovea, and changes in vessel density in the SCP and DCP, which was more pronounced in the period from 1 to 6 months after surgery. The correlation of the changes in the parameters is higher in type 2 of FTMH closure than in type 1 of FTMH closure.Results:. Subgroups with type 1 and type 2 FTMH closure included 67 and 26 eyes, respectively. Type 2 FTMH closure showed lower vascular density in the DCP before (p=0.02) and 6 months after surgery (p=0.03), lower BCVA before surgery (p=0.03), 1 and 6 months after surgery (p <0.001), lower RS at the fixation point before and after surgery (p<0.002).Conclusion. In type 2 macular hole closure, postoperative changes in retinal perfusion have a more pronounced impact on functional recovery of the fovea, especially in the late postoperative period.

Effect of enhanced monofocal intraocular lenses on glaucoma patients' foveal threshold.

We investigated the effect of enhanced monofocal intraocular lenses (IOL) (TECNIS Eyhance DIB00V) on retinal sensitivity in glaucoma patients after cataract surgery by comparing results with of such patients implanted with non-enhanced monofocal intraocular lenses (TECNIS ZCB00V). This was a multi-facility retrospective study of glaucoma patients who had undergone cataract surgery. We measured the value of the foveal threshold with a Humphrey visual field analyzer before and after cataract surgery and considered this value to represent the sensitivity of the retina. As a sub-analysis, we also compared the mean deviation (MD), pattern standard deviation (PSD), thickness of ganglion cell complex (GCC), and best corrected visual acuity (BCVA) before and after surgery. We used t-tests to determine statistical differences between lens groups. We included 60 glaucoma patients (104 eyes) who underwent cataract surgery: enhanced group, n = 58 eyes; non-enhanced group, n = 46 eyes. In both groups, cataract surgery improved the retinal sensitivity (p < 0.001), MD (p < 0.001) and BCVA (p < 0.001). The postoperative foveal thresholds did not significantly differ by lens type (p = 0.673), at 34.41 ± 2.44dB in the enhanced group and 34.61 ± 2.19dB in the non-enhanced group. Likewise, there was no significant difference (p = 0.942) among advanced glaucoma patients, with postoperative foveal thresholds of 33.08 ± 2.35dB and 33.17 ± 3.45dB in the enhanced and non-enhanced, respectively. Implantation of enhanced monofocal IOLs in glaucoma patients did not result in any apparent loss of sensitivity compared with non-enhanced monofocal lens implantation.

A pilot study : retinal sensitivity change in neovascular age-related macular degeneration patients with better baseline visual acuity

This study evaluated changes in retinal sensitivity (RS) during aflibercept treatment in neovascular age-related macular degeneration (nAMD) patients with good vision. Treatment-naive nAMD patients with visual acuity better than 20/40 were treated with an aflibercept loading regiment, and RS was measured using the MAIA microperimetry device. The study examined RS differences based on visit, region, adjacent local pathology, outer retinal changes and optical coherence tomography angiography (OCTA) data were investigated. Twelve patients completed the protocol. Mean RS improved from 17.9 (3.9) µm at baseline to 20.4 (4.7) µm at final visit, while best-corrected visual acuity (BCVA) did not change. (P = 0.041) RS at baseline is worst in the presence of intraretinal fluid (IRF) and improved after treatment for all retinal pathologies except IRF. RS improvement occurred even with initial outer retinal damage. A Linear mixed model showed subretinal hyperreflective material, baseline IRF height, outer retinal integrity, fibrovascular pigment epithelial detachment height, and local choroidal vascular index as factors associated with RS. In conclusion, RS improved with aflibercept treatment in nAMD eyes with good initial visual acuity, despite no change in BCVA, except when IRF was present.

Comparison of Vessel Density and Retinal Sensitivity After Scleral Buckling and Phacovitrectomy in the Management of Macula-on Primary Rhegmatogenous Retinal Detachment.

The choice of surgical method for rhegmatogenous retinal detachment (RRD) may have a significant impact on the retina. In this study, we aimed to compare retinal function and structure after scleral buckling (SB) and phacovitrectomy (phaco-PPV) for macula-on RRD. This cross-sectional study included patients who underwent anatomically successful repair of macula-on RRD managed with SB (n=35) and phaco-PPV (n=35) between 2019-2023. All participants were examined within 6-20 months of surgery to evaluate the retinal structure using spectral domain optical coherence tomography (SD-OCT) and vessel density (VD) by OCT angiography (OCTA). Best-corrected visual acuity (BCVA) and microperimetry (MP) tests were used to assess the retinal function. Analysis of the microvascular network with OCTA between eyes after surgery and healthy eyes showed a decrease in VD. Significant changes in the superficial vascular plexus (SVP) and deep vascular plexus (DVP) were observed only in eyes after SB surgery (p <0.001 and p=0.02, respectively). Analysis of retinal function assessed by MP showed a significant decrease (p<0.05) in retinal sensitivity after phaco-PPV (24.81±2.25 dB) and SB (24.18±2.14 dB) operations compared to the healthy control group (25.97 ± 1.51 dB), whereas postoperative BCVA showed no differences (p>0.05). Changes in retinal sensitivity were accompanied by impairment of the microvascular network in the eyes after SB and phaco-PPV surgeries due to macula-on RRD. Disorders were more pronounced in eyes following SB surgery, possibly secondary to mechanical stress.

Bax expression impacts postnatal retinal vascular development and hyperoxia sensitivity

Apoptosis plays prominent roles during organ development, maturation and homeostasis. In the retina, Bcl-2 family members function through the intrinsic cell death pathway with vital roles during vascular development and hyperoxia-mediated vessel obliteration during oxygen induced ischemic retinopathy (OIR). Bim, a BH3 only protein Bcl-2 family member, binds and activates Bax and/or Bak to facilitate apoptosis. In some systems deletion of both Bax and Bak are required to prevent cell loss, such as regression of ocular hyaloid vasculature. We previously showed Bim expression significantly impacts normal retinal vascular development and sensitivity to hyperoxia. Mice deficient in Bim (Bim-/-) show increased retinal vascular density and are protected from hyperoxia mediated vessel obliteration. Since Bim activates Bax, here we determined the impact lack of Bax expression has on these processes. Compared to Bax+/+ mice, retinas from Bax-/- mice had significantly increased numbers of retinal endothelial cells and pericytes. We also demonstrated that hyperoxia-mediated vessel obliteration during OIR was significantly decreased in the absence of Bax. Although the increased endothelial cell numbers were comparable to that of Bim-/- mice, the increased numbers of pericytes were not to the extent noted in Bim-/- mice. These changes were supported by partial protection of retinal vessels from hyperoxia in Bax-/- mice compared to that noted in Bim-/- mice. Thus, Bim-Bax driven pathway is sufficient to remove excess endothelial cells but not pericytes during postnatal retinal vascularization and hyperoxia-mediated vessel obliteration. Thus, additional Bim-mediated pathway(s) are required for removal of pericytes and hyperoxia-mediated vessel obliteration.

Effects of elevated intraocular pressure on alpha ganglion cells in experimental glaucoma mice

Glaucoma is a leading cause of blindness worldwide and glaucoma patients exhibit an early diffuse loss of retinal sensitivity followed by focal loss of RGCs. Combining some previous published results and some new data, this paper provides our current view on how high IOP (H-IOP) affects the light response sensitivity of a subset of RGCs, the alpha-ganglion cells (αGCs), as well as their presynaptic bipolar cells (DBCs and HBCs) and A2 amacrine cells (AIIACs) in dark-adapted mouse retinas. Our data demonstrate that H-IOP in experimental glaucoma mice significantly decreases light-evoked spike response sensitivity of sONαGCs and sOFFαGCs (i.e., raises thresholds by 1.5–2.5 log units), but not that of the tONαGCs and tOFFαGCs. The sensitivity loss in sONαGCs and sOFFαGCs is mediated by a H-IOP induced suppression of AIIAC response which is caused by a decrease of transmission efficacy of the DBCR→AIIAC synapse. We also provide evidence supporting the hypothesis that BK channels in the A17AC→DBCR feedback synapse are the H-IOP sensor that regulates the DBCR→AIIAC synaptic efficacy, as BK channel blocker IBTX mimics the action of H-IOP. Our results provide useful information for designing strategies for early detection and possible treatments of glaucoma as physiological changes occur before irreversible structural damage.

Vision at high latitudes: High sensitivity without specific boreal adaptations in photoreception in reindeer (Rangifer tarandus L.)

Abstract The light climate at high latitudes, in particular the extended twilight of winter and the reduced diel variation in light level in midsummer and midwinter, potentially constrains visual function and the synchronisation of temporal organisation in polar species. In this paper, we describe the temporal pattern and variation in the spectral composition and brightness of skylight (daylight, twilight, moonlight, starlight, airglow and aurorae) at high latitudes and review photoreception of reindeer/caribou (Rangifer tarandus; ‘Rangifer’) which is one of the few polar resident species for which data are available. Experimental data indicate that the rods of Rangifer may be stimulated by levels of ambient light lower than those occurring during astronomical twilight (solar angle &lt;−18°). Several features of the eyes of Rangifer contribute to their visual capability under extended twilight. These include transmission of UV through the optical media, which enables the animals to exploit the shorter wavelengths characteristic of twilight, and a shift in the peak spectral reflectance of the tapetum lucidum (TL) from around 640 nm in summer to around 450 nm in winter, which increases retinal illumination at short wavelengths. Enhanced sensitivity to short wavelengths is likely to enhance the contrast of some objects and hence the ability of Rangifer to discriminate forage plants and to detect other animals (conspecifics or predators) against a snowy background under low illuminance. There is, nevertheless, currently no evidence of any specific boreal adaptation in their visual system: (i) The eyes of Rangifer, and by inference the area of the dilated pupil, are no larger than expected based on the allometry of eye size in ruminants. (ii) There is no evidence of a change in the spectral sensitivity of photoreceptors associated with detection of UVa. (iii) Transmission of UV through the anterior eye is not unique to Rangifer. (iv) The blue shift in the reflectance of the winter TL appears to be a passive response to prolonged dilation of the pupil and there is no a priori reason not to predict the same response in other large ungulates exposed to low light levels. (v) There is no conclusive evidence of a seasonal shift in absolute retinal sensitivity in Rangifer. (vi) Weak circadian organisation in Rangifer has tentatively been linked to mutations within the circadian molecular clockwork but it remains unclear to what extent this represents a specific adaptation to high latitude. Read the free Plain Language Summary for this article on the Journal blog.

Subtyping stage 3 epiretinal membrane: a comprehensive study of ectopic inner foveal layers architecture and its clinical implications

AimsTo evaluate the visual function and foveal architecture in patients with stage 3 idiopathic epiretinal membrane (iERM).MethodsA cross-sectional observational study included 56 eyes of 52 patients with stage 3 iERM....

Optical Coherence Tomography Split-Spectrum Amplitude-Decorrelation Optoretinography Detects Early Central Cone Photoreceptor Dysfunction in Retinal Dystrophies.

To investigate if split-spectrum amplitude-decorrelation optoretinography (SSADOR) can detect and measure macular cone dysfunction in inherited retinal dystrophies (IRDs). This study was a case series of participants presenting with various IRD pathologies. Participants were recruited from the Ophthalmic Genetics clinic at the Casey Eye Institute from February to August 2023. Multimodal and SSADOR imaging was obtained in all cases. We recruited nine participants, including four with macular dystrophy, one with fundus flavimaculatus, one with cone dystrophy, and three with retinitis pigmentosa. SSADOR decorrelation maps identified areas of cone functional impairment consistent with disease phenotypes. A correlation between the SSADOR signal and retinal sensitivity measured by microperimetry within the central 20° diameter area was observed. Additionally, SSADOR was able to demonstrate a decreased signal in mild cases when microperimetry measurements were still normal but subtle changes were also apparent on structural OCT. SSADOR is sensitive at detecting functional changes in macular cones, even prior to abnormalities in perimetry testing. We highlight the potential benefits of this innovative technology for the early detection of cone dysfunction and their potential contributions to earlier diagnosis and more accurate monitoring of progression. SSADOR is an innovative technology that detects early macular cone function changes, allowing for early diagnosis and precise monitoring of cone dysfunction progression. By serving as a potential clinical trial endpoint, SSADOR facilitates the translation of scientific findings into practical applications, ultimately improving patient care and outcomes.

Short-term efficacy of photobiomodulation in early and intermediate age-related macular degeneration: the PBM4AMD study.

This independent prospective study evaluated the short-term effects and safety of photobiomodulation (PBM) in early and intermediate age-related macular degeneration. patients were treated with PBM in one eye. Functional parameters and drusen volume were measured at one (W4), three- (W12) and six-months (W24) after PBM. The study included 38 subjects who completed the PBM protocol. Two patients developed macular neovascularization during the study period. Best corrected visual acuity improved from 77.82 ± 5.83 ETDRS letters at baseline to 82.44 ± 5.67 at W12 (p < 0.01), then declined to 80.05 ± 5.79 at W24 (p < 0.01 vs. baseline). Low luminance visual acuity showed a similar pattern, improving from 61.18 ± 8.58 ETDRS letters at baseline to 66.33 ± 8.55 at W12 (p < 0.01), and decreasing to 62.05 ± 9.71 at W24 (p = 0.02). Contrast sensitivity improved at W12 (20.11 ± 9.23ETDRS letters, p < 0.01), but returned to baseline by W24 (16.45 ± 9.12, p = 0.5). Scotopic microperimetry showed a decrease in mean absolute retinal sensitivity from 9.24 ± 3.44 dB to 7.47 ± 4.41 dB at W24 (p < 0.01), while relative sensitivity decreased only at W24 (p = 0.04). Drusen volume decreased at W4 (0.018 ± 0.009 mm3, p < 0.01) and W12 (0.017 ± 0.009 mm3, p < 0.01), with a slight increase at W24 (0.019 ± 0.012 mm3, p = 0.154). PBM resulted in temporary improvements in visual function and a reduction in drusen volume, but these effects were not sustained at six months. The long-term efficacy and impact on disease progression are uncertain, necessitating further research to confirm these findings and determine optimal patient selection.

Internal Limiting Membrane Peeling for Large Macular Holes Induces Only Structural Remodeling without Functional Impairment Over 12 Years

To evaluate the very long-term functional and structural outcomes of internal limiting membrane (ILM) peeling for full-thickness macular holes (FTMH). Observational case series nested within a multicenter, randomized, controlled clinical trial (RCT) (ClinicalTrials.gov: NCT00190190). Patients who underwent vitrectomy with or without ILM peeling for an idiopathic large FTMH in a tertiary ophthalmology center, with a minimum follow-up of 10 years after surgery. Review of charts, spectral-domain OCT (SD-OCT) scans, OCT angiography (OCTA) scans, and microperimetry of patients originally enrolled in the RCT. Primary outcome was functional assessment in both groups (ILM peeling or not) including the retinal sensitivity (RS), distance and near best-corrected visual acuity (BCVA), and number of eyes achieving ≥0.3 logarithm of the minimum angle of resolution >10 years after surgery. Secondary outcomes were structural assessment in the entire 3× 3-mm and 6× 6-mm areas, and regionally in the different areas of the ETDRS grid: OCT and OCTA biomarkers in both groups and fellow eyes. Thirteen eyes of 13 patients with a mean follow-up of 12 ± 0.73 years were included. The mean RS and BCVA, or visual improvement did not differ between ILM peeling (n= 8) and no peeling (n= 5) (all P > 0.05). The dissociated optic nerve fiber layers on en face OCT were only observed in eyes with ILM peeling, predominantly in temporal parafoveal (20%) and perifoveal (19%) rings. The mean total retinal thickness and inner retinal thickness in the parafoveal ring were significantly lower in peeled eyes (309 ± 11 μm and 94 ± 9 μm respectively) versus nonpeeled eyes (330 ± 21 μm and 108 ± 11 μm respectively; P= 0.037 and P= 0.040), without significant difference in ganglion cell or retinal nerve fiber layers. Accordingly, the mean superficial capillary plexus density in the parafoveal ring was significantly lower in eyes with peeling versus without (39.65 ± 3.76 % versus 47.22 ± 4.00; P= 0.005). The mean foveal avascular zone area was smaller in eyes with peeling versus without (0.24 ± 0.05 mm2 vs. 0.42 ± 0.13 mm2, respectively, P= 0.005). Despite persistent structural changes especially in the parafoveal ring, ILM peeling for idiopathic large FTMH did not seem to impact long-term RS or BCVA over 12 years. Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Peripapillary retinal nerve fibre layer thinning in patients with X-linked retinoschisis

AimsTo assess peripapillary retinal nerve fibre layer (pRNFL) thickness in patients with X-linked retinoschisis (XLRS), as pRNFL thinning may limit functional improvements in gene therapy trials.MethodsThis retrospective multicentre study included...

Comparison of two laser power levels in the subthreshold micropulse yellow laser treatment of acute central serous chorioretinopathy

AimsTo compare the efficacy of two power levels in the 577 nm sub-threshold micro pulse laser (SML) treatment of acute central serous chorioretinopathy (aCSC). MethodsA retrospective comparative study was conducted. A total of 65 patients (65 eyes) with aCSC were enrolled. Of which, 32 patients received low power treatment and 33 patients received high power treatment of 577 nm SML. Best-corrected visual acuity (BCVA), central macular thickness (CMT), fundus-monitored microperimetry and height of subfoveal choroidal thickness (SFCT) as well as subretinal fluid (SRF) were evaluated at baseline and 3 months. ResultsThe height of SFCT and retinal sensitivity in the low power treatment group was significantly better than that in the high power treatment group at 4 weeks (all p < 0.001). Mean BCVA improved from baseline to 3 months after treatments but with no significant difference between the two groups after 3 months (p > 0.05). In the low power group, the CMT decreased from 379.76 ± 139.23 μm at baseline to 176.56 ± 37.78 μm at 3 months, and in the high power group, the CMT decreased from 364.97 ± 143.08 at baseline to 191.77 ± 38.26 μm at 3 months. There was no significant difference at 3 months between the two groups (p > 0.05). Similar results were also found in term of SRF. ConclusionsTimely intervention with 577 nm SML with low power treatment can improve visual acuity, and included anatomic success without adverse events.

Assessment of ganglion cell complex thickness and its correlation with retinal sensitivity using microperimetry 6 months after epiretinal membrane surgery

PurposeTo verify the correlation between the full-macular and the ganglion cell complex (GCC) thickness measurements and retinal sensitivity (RS) assessed by microperimetry (MP) 6 months after surgical peeling for idiopathic epiretinal membrane (ERM).MethodsForty-three were submitted to pars-plana posterior vitrectomy (PPV) with concomitant peeling of internal limiting membrane (ILM) for idiopathic ERM treatment. Best-corrected visual acuity (BCVA) and 3D volumetric high-definition optical coherence tomography (OCT) imaging were preoperatively acquired. Six months after the surgery, BCVA, OCT imaging, and RS measured by MP were assessed. For the OCT parameters, we analyzed both the full-macular and the ganglion cell layer complex (GCC) thicknesses. The MP parameters tested were 44 points covering 20 central degrees (6 mm), with direct correspondence with the nine sectors of the OCT-ETDRS map. This approach enables the direct topographic correlation between the structure and functional measurements. The OCT and MP exam measurements were also performed in 43 eyes of age-matched healthy controls. Correlations between BCVA, RS, and OCT parameters were examined.Results All patients exhibited a substantial improvement in visual acuity following surgery. The RS parameters were significantly lower in patients compared to the controls. The full-macular thickness measurements were thicker than controls preoperatively and significantly reduced postoperatively; however, remaining significantly higher than controls, in the 4 inner sectors, at the fovea and for the average macular thickness. Preoperative GCC measurements were higher than those in controls. There was a significant reduction in GCC thickness in all sectors postoperatively, especially in the outer sectors, as well as in the average macular thickness. A positive correlation was found between full-macular and GCC thickness and RS postoperatively in several sectors.ConclusionsOur results demonstrate that ERM peeling can improve visual acuity in the postoperative period. However, RS may not fully restore, remaining significantly lower when compared to the controls. Both full-macular and GCC thickness measurements were reduced 6 months after surgery. However, significant thinning of the GCC thickness was observed when compared to the normal control eyes, indicating the occurrence of some degree of ganglion cell layer atrophy. We have demonstrated significant correlations among various OCT thickness parameters, particularly for GCC measurements. We believe that GCC integrity may play an important role in visual function after ERM surgery, and that MP may help better understand the correlations between structural and functional findings following ERM surgery.

Longitudinal assessment of female carriers of choroideremia using multimodal retinal imaging

Background/aimsFemale choroideremia carriers present with a spectrum of disease severity. Unlike in men, the rate of disease progression has not been well characterised in carriers. This longitudinal study aimed to...

XOLARIS: A 24-Month, Prospective, Natural History Study of 201 Participants with Retinitis Pigmentosa GTPase Regulator-Associated X-Linked Retinitis Pigmentosa

ObjectiveTo improve the understanding of the natural disease progression of retinitis pigmentosa GTPase regulator (RPGR)-associated X-linked retinitis pigmentosa (XLRP). DesignA multicenter, prospective, observational natural history study over 24 months. ParticipantsMale participants aged ≥7 years with a pathogenic variant in the RPGR gene, a best-corrected visual acuity (BCVA) score of ≥34 Early Treatment Diabetic Retinopathy Study (ETDRS) letters, and a mean 68-loci retinal sensitivity (assessed by microperimetry) of 0.1–20 decibels (dB). MethodsParticipants were divided into subgroups based on their BCVA score at baseline: 34–73 (lower BCVA) or ≥74 (higher BCVA) ETDRS letters. There were 7 visits over 24 months. Main Outcome MeasuresChange from baseline in BCVA, retinal sensitivity, low luminance visual acuity (LLVA), fixation stability, contrast sensitivity, visual field, anatomical measures, 25-item Visual Function Questionnaire (VFQ-25), intraocular pressure, and adverse events (AEs). ResultsOverall, 201 participants were included. The mean (standard deviation [SD]) age was 30.3 (11.9) years in the lower BCVA subgroup (n=170) and 27.7 (10.1) years in the higher BCVA subgroup (n=31). The study eye baseline mean (SD) BCVA scores were 59.4 (10.30) and 77.3 (3.95) in the lower and higher BCVA subgroups, respectively; the lower BCVA subgroup had lower retinal sensitivity in the study eye at baseline than the higher BCVA subgroup. Over 24 months, there were small observed changes in BCVA, retinal sensitivity, LLVA, fixation, contrast sensitivity, and fundus photography findings. There were observed mean (SD) changes at 24 months in the lower and higher BCVA subgroups of −1.01 (4.67) and 0.03 (5.83) dB-steradians in the volume of full-field hill of vision, −330.6 (869.51) and −122.7 (22.01) μm in distance from foveal center to the nearest border of preserved fundus autofluorescence, −104.3 (277.80) and −207.1 (171.01) μm in central ellipsoid width, and −2.8 (9.7) and −0.6 (7.6) in VFQ-25 composite score, respectively. There was 1 death from completed suicide. There were no ocular serious AEs, and most AEs were mild/moderate. ConclusionsThis study provides evidence of the slow natural progression of XLRP over 24 months in both subgroups and provides important functional, anatomical, and safety data.

Retinal Sensitivity in Macular Subfields and Their Association with Contrast Sensitivity in Early and Intermediate Age-Related Macular Degeneration.

The objective of this study was to evaluate retinal sensitivity in subfields and its association with the novel quantitative contrast sensitivity function (qCSF) in patients with early age-related macular degeneration (eAMD), in patients with intermediate AMD (iAMD), and in healthy controls. In this prospective longitudinal study, retinal sensitivity of a customized 24-point grid was assessed by microperimetry Macular Integrity Assessment (MAIA, CenterVue, Padova, Italy) and divided into different subfields. The Multiple Contrast Vision Meter (Adaptive Sensory Technology, San Diego, CA, USA) was used for qCSF testing. Linear models were used to test the association of functional metrics with variables of interest. 92 study eyes from 92 participants were analyzed (13 eAMD, 31 iAMD, and 48 controls). Microperimetry subfield comparison showed significant differences (p &lt; 0.0001) in the control group between superior and inferior hemifield as well as between central and peripheral subfields. For eAMD, significant differences were found between central and peripheral subfields (p &lt; 0.001) and specific subfields (p &lt; 0.05) and finally for iAMD between specific quadrants (p &lt; 0.05) and specific squares (p &lt; 0.05). Significant associations of retinal sensitivity with qCSF metrics were found for the area underneath the logarithmic contrast sensitivity function, contrast acuity and for the contrast sensitivity at specific spatial frequencies. This study showed significant differences in the evaluated retinal sensitivity subfields, providing localized natural history data for retinal sensitivity in healthy controls and patients with eAMD and iAMD.

Comparison of Microperimetry and Static Perimetry for Evaluating Macular Function and Progression in Retinitis Pigmentosa

To compare the usefulness of microperimetry and static automated perimetry in patients with retinitis pigmentosa (RP), using macular anatomical metrics as a reference. Prospective observational study. Forty-eight eyes of 48 patients with RP in Kyushu University Hospital who underwent microperimetry-3 (MP-3) and Humphrey Field Analyzer (HFA) 10-2 testing ≥3 times during ≥2 years were included. Macular anatomy (ellipsoid zone [EZ] length) was assessed by OCT, and macular function was assessed by MP-3 (mean retinal sensitivity at radii 2°, 4°, and 8°) and HFA10-2 program (mean retinal sensitivity at radii 2°, 4°, and 8°). Correlations between functional and anatomical parameters were analyzed cross sectionally at baseline and longitudinally by comparing the rate of progression. Correlation coefficients between anatomical and functional metrics. The mean age at baseline was 50.1±12.3 years, and the mean follow-up period was 2.8±0.7 years. At baseline, EZ length was significantly correlated with MP-3 mean retinal sensitivity at radii 2°, 4°, and 8° (Spearman's ρ=0.65, 0.84, 0.89; all P<0.005) and HFA10-2 mean retinal sensitivity at radii 2°, 4°, and 8° (Spearman's ρ=0.61, 0.73, 0.78; all P<0.005). Longitudinal analysis showed that the slope of EZ length (-88.92 μm/year) was significantly correlated with the slope of MP-3 retinal sensitivity at 8° radius (-0.62 decibels [dB]/year; Spearman's ρ=0.31, P=0.03) and the slope of HFA retinal sensitivity at 8° radius (-0.60 dB/year; Spearman's ρ=0.43, P<0.005). Both MP-3 and HFA values were cross sectionally well-correlated with EZ length in patients with patients; however, these associations became weaker in the longitudinal analysis. This highlights the need for researchers to explore additional or more sensitive parameters to better monitor RP progression. Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.