Optical coherence tomography findings in three patients with Werner syndrome

Juvenile cataracts frequently occur in the patients with Werner syndrome [14]. In fact, the positive percentage of cataracts is 100% (with a 96% positive percentage for cataracts in both eyes). Therefore, the presence of cataracts is a diagnostic criterion for this disease [7]. Our patients also had the histories of cataract surgery, and two of them already had IOLs in both eyes at their initial visit. Among Japanese people, age-related cataracts are usually observed around the age of 50, with a morbidity less than 10%, and the morbidity increases to 80% or more after the age of 70 [15]. Interestingly, the age of onset of cataracts is extremely young and is usually around 31 years for patients with Werner syndrome [16]. Therefore, most patients consult an ophthalmologist because of poor vision and are diagnosed as having juvenile cataracts of unknown cause at their first visit to an eye clinic. In fact, the causes of juvenile cataracts include diseases that are congenital or atopic dermatitis, as well as diabetes, trauma, and metabolic disorders. Werner syndrome is rarely included in the differential diagnosis because of its rarity.

A national survey in Japan also reported that Werner syndrome was often suggested by dermatologists or plastic surgeons, and not by ophthalmologists [4]. These results suggest that it is necessary to consider measures for early diagnosis and early intervention. The onset of Werner syndrome is usually recognised by bilateral cataracts or grey hair and hair loss, which are usually the first symptoms. However, many of patients and ophthalmologists may not have adequate information to diagnose Werner syndrome. Ophthalmologists often find it difficult to perform a detailed examination of the medical history and genetic testing for Werner syndrome at the time of an ophthalmologic consultation. Therefore, it is difficult for ophthalmologists to make a diagnosis of Werner syndrome.

If a unique ocular finding other than cataracts were observed on ocular examinations in cases of juvenile cataracts in both eyes, we could consider Werner syndrome as a differential diagnosis, and this would lead to an early diagnosis of Werner syndrome. In this report, we documented the cases of three patients with Werner syndrome in whom thinning of the retina and choroid were observed using OCT.

Glaucoma is a well-known disease that causes thinning of the retina owing to the loss of retinal ganglion cells and retinal nerve fiber. The RNFL and GCC start thinning from the early stages of glaucoma, and this finding is useful for its early diagnosis [17]. In addition, aging is considered one of the most important risk factors for the development of glaucoma [18].

The patients in cases 1 and 2 had already been diagnosed with glaucoma and followed up at previous eye clinics before referral to our hospital. And we presume this patient to have glaucoma in left eye upon visual field testing. In fact, Abraham, L.M et al. have also reported primary glaucoma in three siblings with Werner syndrome [19]; however, we could not completely exclude the effect of premature aging as the main feature of this disease.

On the other hand, thinning of the RNFL and GCC also occurs with aging. Leung et al. reported that the cpRNFL thickness naturally decreased by approximately − 0.3 μm per year along with normal aging. An examination showed that the RNFL thickness of the upper area and lower temporal area decreased after the patients reached their 40s [12]. Sung et al. reported that the macular thickness in healthy individuals thinned by approximately − 0.4 μm per year [20], and other studies showed a decrease in the RNFL thickness along with aging [21]. However, the exact cause of this thinning remains unknown.

Therefore, the following question ”Were the changes observed in the cases presented here simply due to the effects of glaucoma?” still remains. We cannot clearly answer this question. Because of that, next, we focussed not only on the retina but also on the choroid in our patients.

The choroid is located between the retina and sclera and is a tissue which is rich in blood vessels and pigments. The choroid can be divided into three layers. The innermost layer is the choriocapillaris, which consists of a dense network of fenestrated capillaries; the second is the Sattler’s layer, which consists of small and medium-sized blood vessels; and the third is the Haller’s layer, which consists of large blood vessels [22]. In healthy individuals, a relationship between choroidal thickness and aging has been reported, and choroidal thickness is known to decrease gradually with aging [23]. Therefore, we focused on the choroidal changes in the OCT images. Considering past literature, the health condition of the patients in Case 1 (44 years old) and Case 2 (57 years old) corresponded to that of a healthy person in their 80s, and the health condition of the patient in Case 3 (47 years old) corresponded to that of a healthy person in their 60s [24]. Other than aging, some factors, such as axial length [25], sex [25], intraocular pressure changes [26], diurnal fluctuations [27], blood glucose levels, and blood pressure treatment [28], have been reported to affect choroidal thickness. However, in our cases, we think that the effect of these factors on choroidal thickness was small, suggesting early age-related changes in the choroid.

Few reports have documented structural retinal changes, especially in the choroid in patients with Werner syndrome, and some cases of complications of glaucoma have also been reported [19]. As described before, the thinning of the cpRNFL and GCC observed on OCT images might be caused not only by an age-related change, but also by a glaucomatous change. However, if we consider choroidal thinning, these retinal and choroidal changes might be due to accelerated aging in patients with Werner syndrome.

When we evaluate age-related retinal and choroidal changes in a healthy human, it is very difficult to follow the changes on OCT images over decades in the same patient. In fact, most of the previous reports on the relationship between aging and choroidal changes are comparative analyses of data measured separately for each age group. However, in Werner syndrome, the same patient can be followed up for several years and we might have the possibility of witnessing the changes similar to those in a healthy human for decades because of the accelerated age-related changes in Werner syndrome. Although more cases and further research are needed in the future, Werner syndrome might be a ‘human retinal/choroidal aging model’ that can help determine aging-related retinal and choroidal changes.

We should describe some limitations of this case report. First, the changes in the choroid and retina might have been due to incidental thinning. Second, these changes might be because of complications, such as glaucoma, which are associated with Werner syndrome. Third, although our cases showed no evidence of diabetic complications, such as diabetic retinopathy, the choroidal and retinal changes could possibly be due to diabetes and the effects of anti-diabetic drugs [29].

Fourth, we could not exclude the effect of atherosclerosis on retinal thickness. It is well known that atherosclerosis, which is an important aspect of Werner syndrome, is associated with reduction of retinal thickness on OCT. For example, previous studies revealed that reduction of retinal thickness is associated with chronic renal failure [30]. No serious atherosclerosis was observed in the fundus of the patients, and they did not have severe renal failure; therefore, we believe that these retinal thickness reductions were not associated with chronic renal failure in our patients.

Finally, the effects of other oral medications, such as blood pressure-lowering drugs, and diurnal fluctuations cannot be excluded.

In our three cases, OCT examination enabled the observation of retinal and choroidal thinning. In order to promote early diagnosis of Werner syndrome, it is necessary to create awareness regarding Werner syndrome among ophthalmologists. When we encounter juvenile cataracts of unknown cause and OCT images show thinning of the retina and choroid unexpected to occur naturally with aging, we should consider Werner syndrome as a differential diagnosis.

留言 (0)

沒有登入
gif