Retinal imaging with adaptive optics scanning laser ophthalmoscopy in unexplained central ring scotoma

Adaptive optics scanning laser ophthalmoscopy allows for noninvasive, in vivo visualization of retinal abnormalities at a cellular level. We herein describe for the first time, to our knowledge, the utility of high-resolution retinal imaging in studying the photoreceptor mosaic in an otherwise unexplained visual disturbance. Imaging of the cone mosaic was performed in a 64-year-old man with a unilateral ringlike paracentral distortion that could not be explained using common clinical imaging instruments. Adaptive optics scanning laser ophthalmoscopy findings revealed a parafoveal circular abnormality of the cone mosaic approximately 3 degrees in diameter that corresponded to the ring of visual disturbance. Visualization of the cone mosaic with adaptive optics scanning laser ophthalmoscopy can reveal photoreceptor damage that may not be detectable with standard imaging devices. Optical axial sectioning of the retina may help in identifying and localizing abnormalities within the retinal layers.     

采用自适应光学扫描激光检眼镜系统观察健康成年人黄斑区视锥细胞的分布

目的：采用自适应光学扫描激光检眼镜(AO-SLO)系统观察不同年龄健康成年人黄斑区视锥细胞的分布，分析其与年龄的相关性。

方法：选取2023-06/07于我院进行健康体检者100例200眼，根据年龄进行分组，其中A组年龄18-30岁，B组年龄31-40岁，C组年龄41-50岁，D组年龄51-65岁，每组各25例50眼。纳入研究对象双眼均行AO-SLO检查，测量视锥细胞密度。

结果：各组研究对象双眼中心凹偏心率3°处2.4°×2.4°范围视锥细胞密度均有差异(P<0.001)，且各区域视锥细胞密度均呈现较为规律的分布特点，均以颞侧视锥细胞密度最高，由高至低依次为颞侧>鼻侧>下方>上方。各组研究对象双眼黄斑区平均视锥细胞密度分别为14144.38±1082.40、13241.24±535.32、12930.29±727.73、10907.50±490.86 cell/mm²(P<0.001)，提示随着年龄的增长，视锥细胞密度呈下降趋势。相关性分析结果显示，纳入研究对象黄斑区平均视锥细胞密度与年龄呈负相关(r=-0.578，P<0.001)。

结论：AO-SLO检查是一种可无创定量检测视锥细胞的方法，健康人群黄斑区视锥细胞密度与年龄呈负相关关系，50岁以上健康人群视锥细胞密度明显降低。     

Rod photoreceptor temporal properties in retinitis pigmentosa

One of the characteristic signs of retinitis pigmentosa (RP) is the progressive loss of night vision. We have previously shown that the gain of rod photoreceptor activation is moderately reduced in some patients with RP, but this decrease in activation kinetics is not sufficient to account for the night blindness. Recently, single rod recording from animal models of RP showed rods under degeneration remain saturated for shorter periods than normal rods; i.e. are less able to sustain the rod photoresponse. Using paired-flash ERG, here we determine whether rod phototransduction inactivation parameters might also be abnormal in patients with RP. Inactivation parameters were derived from 13 subjects with normal vision, 16 patients with adRP, and 16 patients with autosomal recessive/isolate (rec/iso) RP. The adRP cases included 9 patients with rhodopsin mutations and 7 patients with peripherin/RDS mutations. The inactivation phase was derived using a double-flash paradigm, with a test flash of 2.7 log scot td-s followed at varying intervals by a 4.2 log scot td-s probe flash. Derived rod photoresponses to this just-saturating test flash in normal subjects exhibit a critical time to the initiation of recovery (T_sat) of 525 ± 90 (SD) ms. The values of T_sat were 336 ± 104 (SD) ms in patients with adRP (P < 0.001) and 271 ± 45 (SD) ms (P < 0.001) in patients with rec/iso RP. When T_sat values were categorized by mutations, the values were 294 ± 91 (SD) ms (P < 0.001) for rhodopsin mutations, and 389 ± 100 (SD) ms (p = 0.01) for peripherin/RDS mutations. Overall, T_sat in patients with RP was significantly correlated with the amplitude of ISCEV standard rod response (r = 0.56; P < 0.001) and the gain of the activation phase of phototransduction (r = 0.6, P < 0.001). T_sat may be a useful marker for therapeutic efficacy in future clinical trials in RP.     

Adaptive optics scanning laser ophthalmoscopy in fundus imaging, a review and update

Adaptive optics scanning laser ophthalmoscopy (AO-SLO) has been a promising technique in funds imaging with growing popularity. This review firstly gives a brief history of adaptive optics (AO) and AO-SLO. Then it compares AO-SLO with conventional imaging methods (fundus fluorescein angiography, fundus autofluorescence, indocyanine green angiography and optical coherence tomography) and other AO techniques (adaptive optics flood-illumination ophthalmoscopy and adaptive optics optical coherence tomography). Furthermore, an update of current research situation in AO-SLO is made based on different fundus structures as photoreceptors (cones and rods), fundus vessels, retinal pigment epithelium layer, retinal nerve fiber layer, ganglion cell layer and lamina cribrosa. Finally, this review indicates possible research directions of AO-SLO in future.     

Yearly rates of rod and cone functional loss in retinitis pigmentosa and cone-rod dystrophy

ObjectiveTo provide the first measures of the relative rates of rod and cone functional loss in patients with retinitis pigmentosa (RP) or cone-rod dystrophy (CRD).DesignFive-year, prospective natural history study.ParticipantsNinety-six patients (67 with RP and 29 with CRD) retaining measurable rod-mediated visual function and 5 normal subjects were tested at baseline and annually for 4 consecutive years.Main outcome measuresTests of visual function included visual acuity, dark-adaptation thresholds, dark-adapted static perimetry, and rod and cone computer-averaged electroretinograms (ERGs), which were obtained over a range of retinal illuminances. Intervisit variability for each measure was obtained in a subset of patients who were tested twice within a 2-month interval and was used to determine whether an individual patient had shown progression, regression, or no change over a particular study interval.ResultsOver a 4-year interval, a significant number of patients with RP (60%) and CRD (62%) showed a decline in cone ERG amplitude. For rod ERG amplitude, the percentage of patients with RP or CRD showing progression was 64% and 45%, respectively. Although visual acuity, dark-adapted threshold, and rod visual field area also declined significantly over the 4-year period, the mean rate of change and the numbers of patients showing progression on these measures were lower than those for ERG measures. On specialized ERG testing, the yearly change in rod ERG threshold in RP was greater than the yearly change in cone ERG threshold, and the rate of progression varied significantly among inheritance types. For patients with CRD, the yearly change in rod threshold was comparable to the yearly change in cone ERG threshold.ConclusionsThis study helps to define the natural progression of rod-mediated and cone-mediated functional loss in patients with RP and CRD.     

Objective monitoring of papilloedema using confocal scanning laser ophthalmoscopy

Idiopathic intracranial hypertension can cause severe optic nerve damage with irreversible visual loss. Heidelberg retina tomography is a sensitive and reproducible tool that can be used in the monitoring of optic disc swelling due to IIH. We demonstrate that the three-dimensional images produced are easy to interpret, indicate progression or resolution and improve the timing of intervention in multidisciplinary settings by facilitating communication between specialists.     

Anthocyanin can arrest the cone photoreceptor degeneration and act as a novel treatment for retinitis pigmentosa

Retinitis pigmentosa (RP) is a group of heterogeneous inherited retinal diseases that is characterized by primary death rod photoreceptors and the secondary loss of cones. The degeneration of cones causes gradual constriction of visual fields, leaving the central islands that are eventually snuffed out. Studies indicate that the hyperoxia causes oxidative damage in the retina and contributes to the cone death of RP. Moreover, abundant reactive oxidative species (ROS) which are generated in cones may result in mitochondria membrane depolarization, which has been ascribed a central role in the apoptotic process and has been proposed to act as a forward feeding loop for the activation of downstream cascades. Anthocyanin is a potent antioxidant which has been evidenced to be able to counteract oxidative damages, scavenge surplus ROS, and rectify abnormities in the apoptotic cascade. Taken together with its ability to attenuate inflammation which also contributes to the etiology of RP, it is reasonable to hypothesize that the anthocyanin could act as a novel therapeutic strategy to retard or prevent cone degeneration in RP retinas, particularly if the treatment is timed appropriately and delivered efficiently. Future pharmacological investigations will identify the anthocyanin as an effective candidate for PR therapy and refinements of that knowledge would ignite the hope of restoring the visual function in RP patients.     

Optical coherence tomography biomarkers of photoreceptor degeneration in retinitis pigmentosa

Purpose

Several parameters on optical coherence tomography (OCT) have been suggested as biomarkers for photoreceptor degeneration in retinitis pigmentosa (RP). This study is to compare the spatial distribution of the changes of OCT biomarkers in RP patients.

Methods

OCT line scans of the horizontal meridian were conducted in 22 eyes of 22 RP patients and 30 eyes of 30 healthy controls. Longitudinal reflectance profiles were obtained using ImageJ at every 5 pixels. The following parameters on OCT were quantitatively measured: (1) relative optical intensity (ROI) of ellipsoid zone (EZ) and interdigitation zone (IZ); (2) thickness of outer nuclear layer (ONLT), photoreceptor (PRT), inner segment (IST) and outer segment (OST). The variations of these parameters across different regions were analyzed.

Results

From fovea to perifoveal region, all the OCT biomarkers declined before disappeared, except IST and IZ-ROI. There was no identifiable declining zone for the IST and IZ-ROI between the normal and disappeared zones in some patients. The most central biomarker was the reduction of OST and IZ-ROI, followed by the PRT, EZ-ROI, then IST and finally ONLT. All these biomarkers had significant correlations with best-corrected visual acuity, except ONLT.

Conclusion

In retinitis pigmentosa, EZ-ROI, IZ-ROI, PRT, OST, IST and ONLT are valuable biomarkers of photoreceptor degeneration. Changes of OST and IZ-ROI are located most centrally and may be the early biomarkers.