Benign fleck retina refers to an autosomal-recessive condition associated with a distinctive retinal appearance and no apparent visual or electrophysiological deficits.1 Affected individuals are asymptomatic, but fundus examination reveals a striking pattern of diffuse, yellow-white, fleck-like lesions extending to the far periphery of the retina but sparing the foveal region.2, 3, 4, 5 The phenotype associated with benign fleck retina was first described in 1980 in seven affected siblings born to consanguineous parents. 2 A similar clinical appearance was subsequently reported in three unrelated individuals originating from diverse ethnic backgrounds.3, 4, 5 Elucidating the genetic basis of human ocular phenotypes such as that of benign fleck retina remains a major goal because it will provide important insights into the complex biochemistry and cellular physiology of the human eye.

A 22-year-old female who presented with headaches. She gave no history of ophthalmic or systemic disease. On examination her visual acuities were (RE) 6/6 and (LE) 6/6(p) corrected to 6/6 with -0.50 DC 140 in Left eye. The anterior segments of both eyes were normal, and the intraocular pressures were within normal limits. Central and peripheral visual fields did not show any abnormalities, and dark adaptometry was normal. Fundoscopy showed that in both eyes the fundi were invaded by an enormous number of bright white and sometimes yellowish white flecks of variable size and configuration, arranged in a concentric pattern around the posterior fundus and sparing the optic disc, macula, papillomacular area as well as 1-2 disc diameters circular region surrounding the disc and macula. They spread everywhere in the equator and mid and extreme periphery of fundus. The more centrally located flecks appeared sparse, small, round, and dot-like. Others of larger size in the equatorial and peripheral areas varied in shape, being, round, elongate, pisciform, star-shaped, and sometimes circular. The flecks were always discrete, well defined, with almost sinuous margins and a flat or prominent surface. They appeared to be solid and well behind the retinal vascular tree. Throughout the fundus they showed the same mosaic appearance. They spared no area in the periphery. No pigmentary disturbances, calcification or conglomeration was observed, nor were choroidal vessels observed.

Figure 1

Figure 2

[Fluorescein angiography carried out at this time showed that apart from the macula the whole fundus was hyperfluorescent, including the central areas which appeared free of flecks on fundoscopy and white light photography. This indicated there was no close correlation between the site of the flecks and the hyperfluorescent areas, particularly in the central part of the fundus]

Benign familial fleck retina is inherited as an autosomal recessive condition. The term "flecked retina" was introduced by Krill and Klien to describe fundus conditions characterized by multiple yellowish-white lesions of various size and configuration, without vascular or optic nerve abnormalities. Originally this group consisted of four diseases: fundus albipunctatus, fundus flavimaculatus, familial drusen and fleck retina of Kandori. However, far more diseases correspond to the rather vague definition, including primary hereditary ocular diseases such as retinitis punctata albescens or Bietti's crystalline dystrophy, neuro-ophthalmologic syndromes such as Kjellin's syndrome, secundary retinal flecks due to metabolic disorders such as Alport's syndrome, cystinosis, oxalosis or membrano-proliferative glomerulonephritis, iatrogenic retinopathy due to Tamoxifen or Canthaxanthin and carential diseases such as vitamin A deficiency. The precise diagnosis is not only based on the close observation of the fundus, but demands often extensive psychophysical examination of the patient and sometimes of his family.

Massive mosaic hyaline excrescences along the cuticular layer of Bruch's membrane, leading to the appearance of multiple deep yellow to yellowish white lesions of variable size and shape in the fundi have been well known for more than a century.1, 2, 3 Many forms of this condition have been described with different findings, prognosis, and inheritance4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15 . Kril16, 17 regarded all these conditions as fleck retina diseases. He then classified them into 4 groups: fundus albipunctatus, fundus flavimaculatus, familial drusens, and fleck retina of Kandori. This classification with subgrouping according to the severity of the condition seemed to bring order into the confusion that had lasted for a century. In this paper we present a family with flecked retina, with typical fundoscopy picture and normal visual findings. We suggest they belong to a fifth group benign familial fleck retina.

Clinically there was no night blindness or any delay in dark adaptation.

FAF reveals multiple hyperautofluorescent lesions corresponding in location with the flecks. On SD-OCT, discrete deposit accumulation located posterior to the photoreceptor inner/outer segment junction but without disrupting it is observed. Normal full-field and pattern ERGs confirm the diagnosis;15 multifocal ERG may be slightly subnormal in some isopters.16

Recessive mutations in the gene encoding group V phospholipase A₂ (PLA2G5) and mildly elevated low-density lipoprotein and total cholesterol levels have been identified in some individuals with benign fleck retina.17

Benign fleck retina should not be confused with “fleck retina of Kandori.” The latter is associated with large white lesions, possibly atrophic changes, and night-blindness.18 It is not clear if “fleck retina of Kandori” is a genetic condition or even an independent clinical entity.

The main features of the different types of flecked retina disorders reported in the literature are summarised below Table 1

Table 1

FLECK RETINA DISEASE	CHANGES IN FUNDI	FUNCTIONAL DISTURBANCES	MODE OF INHERITANCE
Fundus albipunctatus	Discrete uniform white dots. Night blindness. Dark Autosomal recessive Distribution: over the whole adaptation: normal	slow or Autosomal dominant23 fundus greatest density at monofunctional (only cone midperiphery. No macular threshold) involvement. No pigmentary disturbances or secondary calcification	Discrete uniform white dots. Night blindness. Dark Autosomal recessive Distribution: over the whole adaptation: normal
Fundus flavimaculatus	Round, linear, or pisciform lesions. Distribution: limite to the posterior pole, or extends to the equator. Macula is involved. Network atrophy of retinal pigment epithelium. Choroidal vascular atrophy	Central visual loss, colour vision loss, photophobia, paracentral scotoma, slow dark adaptation	Autosomal recessive
Familial drusen"	Round or oval lesions in almost grape-like clusters. Distribution: concentrated in the posterior polar region. Pigmentary disturbances and secondary calcifications. Macula is almost always involved, may appear oedematous or haemorrhagic	Loss of vision during progressive stages, central scotoma slow dark adaptation	Autosomal dominant
Fleck retina of Kandori	Irregular flecks with great variability in size. Distribution: in the equatorial or between the equatorial and macular region with tendency for confluence. No macular lesions. Disturbance of pigment epithelium	Some night blindness. Initially delayed dark adaptation, recovers to normal value after 30-40 minutes in the dark	Autosomal recessive
Benign familial fleck retina	Round, linear, or pisciform. Distribution: in the whole fundus except the disc and macula. No macular lesions. No tendency for confluence. No pigmentary disturbances	No disturbance of visual function (no symptoms)	Autosomal recessive

Benign familial fleck retina is inherited as an autosomal recessive condition. This is supported by the fact that both sexes were involved and that both parents were free of the disease.

Terry Ernest J. Krill Alex E. Fluorescein Studies in Fundus Flavimaculatus and Drusen American Journal of Ophthalmology 1966 62 1 1 6 0002-9394 10.1016/0002-9394(66)91668-0 Elsevier BV https://dx.doi.org/10.1016/0002-9394(66)91668-0 Deutman A F The Hereditary Dystrophies of the Posterior Pole Van Gorcum Assen 1971 484 484 Duke-Elder S Diseases of the retina. System of Ophthalmology 1967 10 10 Lauber H Die sigenaunte Retinitis punctata albescens Klin Monatsbl Augenheilkd 1910 48 133 181 Kandori F Very rare cases of congenital non-progressive night blindness with fleck retina Jpn J Ophthalmol 1959 13 384 390 Krill A E Hereditary Retinal and Choroidal Diseases: Flecked Retina Diseases. Hagerstown: Harper and Row 1877 739 819 Muller H Untersuchungen uber die glashaute des Auges, insbesondere die glaslamelle der Choroidea und ihre senilen Veranderungen Albrecht von Graefes Arch Klin Ophthalmol 1856 2 1 63 Wedl C Grundzuge der pathologischen Histologie Gerold Wien 1854 825 825 Franceschetti A Francois J Fundus flavimaculatus Arch Ophthalmol (Paris) 1965 25 505 535 Mooren A Funf Lustren Ophthalmologischer Wirksamkeit 1882 Bergmann Wiesbaden 311 311 Kempt H Amalric P Remky H Fundus flavimaculatus Klin Monatsbl Augenheilkd 1967 150 625 661 Newell F W Krill A E Farkas T C Drusen and fundus flavimaculatus: clinical, functional and histological characteristics Trans Am Acad Ophthalmol Otolaryngol 1972 76 88 100 Brini A Fundus Bull Soc Ophthalmol Fr 1966 66 222 261 Babel J Le Arch Ophthalmol 1972 32 109 130 CARR R. E. Fundus Flavimaculatus Archives of Ophthalmology 1965 74 2 163 168 0003-9950 10.1001/archopht.1965.00970040165007 American Medical Association (AMA) https://dx.doi.org/10.1001/archopht.1965.00970040165007 Donders F. C. Beiträge zur pathologischen Anatomie des Auges Albrecht von Graefes Archiv für Ophthalmologie 1855 2 1 106 118 0721-8494, 1435-702X 10.1007/bf02720791 Springer Science and Business Media LLC https://dx.doi.org/10.1007/bf02720791 Doyne R W Peculiar condition of choroiditis occurring in several members of the same family Trans Ophthalmol Soc UK 1899 19 71 71 KRILL A. E. KLIEN B. A. Flecked Retina Syndrome Archives of Ophthalmology 1965 74 4 496 508 0003-9950 10.1001/archopht.1965.00970040498011 American Medical Association (AMA) https://dx.doi.org/10.1001/archopht.1965.00970040498011