正常與漸進性視網膜萎縮症貴賓犬之視網膜形態、 基因檢測及眼底影像半自動化分析之探討

Abstract

漸進性視桿—視錐退化症（progressive rod-cone degeneration, PRCD）為貴賓犬中最常見的漸進性視網膜退化症（progressive retinal atrophy, PRA）類型，屬於晚發性遺傳性視網膜疾病。本研究旨在調查台灣玩具型與迷你型貴賓犬之PRCD 盛行率與突變等位基因頻率，結合完整眼科檢查與眼底攝影，探討PRCD基因型與臨床表現之關聯，並利用半自動化影像分析方法量化不同基因型犬隻的視網膜血管參數，同時建立犬隻正常參考區間。研究共收集107隻貴賓犬（玩具貴賓74隻、迷你貴賓33隻）進行眼科臨床檢查及眼底攝影，並以口腔黏膜採樣進行 PRCD基因檢測。眼底影像透過結合深度學習視神經盤定位與血管分割的半自動化分析流程，計算視網膜動脈直徑（RAD）、靜脈直徑（RVD）與動靜脈比值（AVR）。結果顯示，玩具貴賓犬之PRCD盛行率為10.8%，迷你貴賓犬為9.1%，其突變等位基因頻率分別為0.216與0.182，突變基因攜帶者（HET；G/A）在兩品種皆佔約20%。影像分析共納入366張眼底影像，取得13789筆血管直徑量測資料，最終建立198隻眼睛的代表性血管參數。PRCD突變同型合子（AFF；A/A）犬隻之RAD與RVD皆呈現明顯變細，而AVR未出現顯著差異，於未受PRCD影響犬隻也成功建立RAD、RVD 及 AVR 的正常參考區間。少數犬隻則出現基因型與眼底表現不一致之情形。總結來說，PRCD 在台灣玩具型與迷你型貴賓犬中具有相當高的遺傳負擔，約五分之一犬隻為突變基因帶因者，顯示基因篩檢對疾病預防與育種管理的重要性。PRCD 受影響犬隻出現明顯的視網膜血管變細，顯示視網膜血管直徑具有作為臨床評估視網膜退化程度之客觀輔助指標的潛力。

Progressive rod–cone degeneration (PRCD) is the most common form of progressive retinal atrophy (PRA) in Poodles and is classified as a late-onset inherited retinal disease. The aims of this study were to determine the prevalence and mutant allele frequency of PRCD in Toy and Miniature Poodles in Taiwan, to investigate the relationship between PRCD genotype and clinical phenotype through comprehensive ophthalmic examinations and fundus photography, and to quantitatively assess retinal vascular parameters across different PRCD genotypes using a semi-automated image analysis approach, while establishing normative reference intervals for Poodles. A total of 107 Poodles (74 Toy Poodles and 33 Miniature Poodles) were enrolled and underwent complete ophthalmic examinations and fundus photography. PRCD genotyping was performed using buccal mucosal swab samples. Fundus images were analyzed using a semi-automated pipeline incorporating deep learning–based optic nerve head localization and retinal vessel segmentation to calculate retinal arteriolar diameter (RAD), retinal venular diameter (RVD), and arteriole-to-venule ratio (AVR). The prevalence of PRCD was 10.8% in Toy Poodles and 9.1% in Miniature Poodles, with corresponding mutant allele frequencies of 0.216 and 0.182, respectively. Heterozygous carriers (HET; G/A) accounted for approximately 20% of dogs in both breeds. A total of 366 fundus images were included for image analysis, yielding 13,789 individual vessel diameter measurements and representative vascular parameters from 198 eyes. PRCD-affected dogs (AFF; A/A) exhibited significant narrowing of both RAD and RVD compared with PRCD-unaffected dogs, whereas no significant difference in AVR was observed. Normative reference intervals for RAD, RVD, and AVR were successfully established from PRCD-unaffected dogs. A small number of dogs demonstrated discordance between genotype and funduscopic phenotype. In conclusion, PRCD represents a substantial genetic burden in Toy and Miniature Poodles in Taiwan, with approximately one-fifth of dogs being carriers, underscoring the importance of genetic screening for disease prevention and breeding management. Marked retinal vascular attenuation in PRCD-affected dogs suggests that retinal vessel diameter measurements may serve as an objective adjunctive indicator for clinical assessment of retinal degeneration.