Authors from Japan attempt to correlate retinal vascular changes with cavernosal arterial blood flow. They studied patients with erectile dysfunction, but excluded patients with previous pelvic surgery, pelvic injury or diabetes. They found that penile changes can be anticipated from retinal vascular changes seen on fundoscopy.
To assess the correlation between retinal vascular findings and penile cavernosal arterial blood flow, as it is probable that systemic atherosclerotic vascular disease is important in male erectile dysfunction (ED), and being systemic, it might be possible to evaluate the extent of atherosclerosis from retinal vascular findings.
PATIENTS AND METHODS
The study included 75 patients with ED; any with a history of pelvic injury, pelvic surgery, or diabetes mellitus were excluded. All patients gave fully informed consent. Ocular fundus photographs were taken with an automatic-focus fundus camera under amydriatic conditions. Three ophthalmologists, unaware of the patients’ detailed data, evaluated the photographs using Hyman's classification to evaluate retinal vascular findings. Blood flow in the penile cavernosal artery was measured with colour Doppler ultrasonography, and the peak systolic velocity used as a haemodynamic variable. Correlations among the peak systolic velocity, retinal vascular findings and vascular risk factors (including hypertension, age, cigarette smoking, and hyperlipidaemia) were investigated using multivariate analysis.
Of the 75 patients, 72 (96%) had both right and left retinal vascular images of sufficient quality for evaluation; 37 were classified as normal and 35 as Grade I, while no patient was Grade II. From a logistic regression multivariate analysis, the peak systolic velocity was the only significant factor correlating with retinal vascular findings, with an odds ratio of 3.34. In contrast, hypertension, age, cigarette smoking and hyperlipidaemia did not correlate significantly with the retinal vascular findings. Similarly, the retinal vascular finding was the only significant factor correlating with the peak systolic velocity of cavernosal blood flow (odds ratio 3.28) and again hypertension, age, cigarette smoking and hyperlipidaemia were not significant factors.
These findings support the assumption that penile erectile function is one of the diseases of atherosclerosis, and emerges nearly simultaneously with retinal vascular disease. It is possible to predict penile arterial conditions in patients with ED from their retinal vascular findings. Thus, amydriatic fundoscopy, a simple practical examination, may be helpful for primary physicians in diagnosing and treating ED.
peak systolic velocity.
The invention of ocular fundoscopy by Helmholtz made it possible to observe retinal vessels directly . Various aspects of retinal vascular findings and their clinical implications have since been investigated, and these studies clarified that a retinal vascular abnormality is one of the predictors of cardiovascular disease . At present, fundoscopy is used routinely as a diagnostic tool for atherosclerosis, not only by ophthalmologists but also by primary physicians. As penile erectile function is vulnerable to peripheral circulatory disturbance, atherosclerosis is thought to be one important cause of erectile dysfunction (ED). Arteriogenic ED is thought to be a possible marker of coronary heart disease and therefore might be a predictor of systemic atherosclerosis . We hypothesised that there might be some relationship between the retinal vascular and penile vascular conditions, and thus assessed the arterial conditions of the eye and penis in men with ED.
PATIENTS AND METHODS
Participants were patients who visited our clinic complaining of male ED from June to October 2002. Patients with a history of pelvic injury or pelvic surgery were excluded, as were those with diabetes, because they might have had diabetes-specific retinopathy. Among the remaining 85 patients, 75 agreed to participate, giving fully informed consent; the study was conducted with approval from the ethical committee of our hospital (approval number 02–001).
The relationships between the penile cavernosal and retinal vascular conditions and patient factors were examined, the latter being age, hypertension, hyperlipidaemia and cigarette smoking. Blood flow in the penile cavernosal artery was measured using colour Doppler ultrasonography; 10 µg of prostaglandin E1 was injected into the corpus cavernosum and the patients then asked to stimulate their penis. Doppler ultrasonography was then applied 3–10 min after intracavernosal injection while the patient was supine. After total scanning of the cavernosal body, the peak systolic velocity (PSV) of both cavernosal arteries was measured at the base of the penis. The Doppler examinations were applied twice at an interval of 1–4 weeks, and the higher mean PSV recorded then used in the analysis. One urologist carried out all the Doppler examinations. The PSV of the cavernosal blood flow was taken as the haemodynamic variable; when the mean right and left PSV was ≥ 25 cm/s, the cavernosal arterial blood flow was considered normal.
Ocular fundus photographs were taken with an automatic focus fundus camera under amydriatic conditions (Fig 1a,b; CR-45UAF, Canon, Tokyo). Three ophthalmologists unaware of the patients’ detailed data evaluated the photographs using Hyman's classification , i.e. vascular findings including arteriolar stenosis, or localized constriction or arteriovenous nicking, were classified as Grade I. Grade II was assigned when there was a severe vascular condition, e.g. haemorrhage, exudate or disc oedema. When there were no abnormal findings in either eye, the retinal vascular findings were considered normal.
The Mann–Whitney U-test and logistic regression were used to assess the results. Correlations among the PSV, retinal vascular findings and vascular risk factors were investigated using multivariate analysis. If a patient had a history of hypertension or hyperlipidaemia they were considered ‘positive’ regardless of treatment method. Patients were classified into 10-year age groups. For cigarette smoking, if the patient's Brinkman index (daily consumption × years) was > 200 the factor was considered positive. In all tests P < 0.05 was considered to indicate significance.
The evaluation of penile cavernosal arterial blood flow by colour Doppler ultrasonography was successful in all 75 patients and 72 (96%) had both right and left retinal vascular images of sufficient quality for evaluation. The three patients who did not were one with severe myopia, one with a congenital small pupil and one with myopic retino-choroidal atrophy. The 72 patients with clear fundus images were included in the analysis (median age 49.5 years, range 22–74). The three ophthalmologists agreed on the diagnosis of retinal findings in all 72 patients; 37 were classified as normal and 35 as Grade I, with no patient Grade II. The mean (range) PSV of the patients with normal retinal findings was 35.3 (10.2–76.5) cm/s, and in those with a Grade I fundus was 27.9 (13.0–27.9) cm/s, which was a statistically significant difference.
There were 50 patients whose mean PSV value of the right and left cavernosal arteries was ≥ 25 cm/s (Table 1); the other 22 patients were assumed to have cavernosal arterial insufficiency. The distribution of patients with normal and abnormal retinal conditions in each PSV category is shown in Table 1.
|Mean (sd) variable||Normal||Abnormal|
|No. of patients||50||22|
|Mean (sd) [range] PSV, cm/s*||36.8 (1.3) [26.1–76.5]||20.1 (3.8) [10.2–24.9]|
The multivariate analysis, with retinal vascular findings as the dependent variable and PSV, hypertension, age, cigarette smoking and hyperlipidaemia as independent variables, is shown in Table 2; PSV was the only significant factor correlating with retinal vascular findings. When the PSV was assigned as the dependent variable in multivariate analysis, the retinal vascular finding was the only significant factor correlating with it (Table 2). The relationship between fundoscopy and a low PSV gave the following values: sensitivity (15/22, 68%), specificity (30/50, 60%), accuracy (45/72, 63%), positive predictive value (15/35, 43%) and negative predictive value (30/37, 81%).
|Variables||n (%)||P||Odds ratio (95% CI)|
|< 25||22 (31)||0.03||3.34 (1.12–9.97)|
|≥ 25||50 (69)|
|< 39||25 (35)||0.09||1.40 (0.95–2.04)|
|≥ 70||10 (14)|
|+ve||18 (25)||0.82||1.13 (0.36–3.54)|
|+ve||27 (38)||0.38||1.62 (0.55–4.78)|
|+ve||13 (18)||0.95||0.96 (0.26–3.48)|
|Normal||37 (51)||0.03||3.28 (1.11–9.69)|
|Cigarette smoking||0.89||0.93 (0.34–2.54)|
Although it is 150 years since the invention of ocular fundoscopy, the clinical classification of retinal vascular findings remains controversial [5–7], but fundoscopy is the only assessment that directly detects morphological changes in the arterioles of humans [8–11]. Erectile function is vulnerable to psychological, circulatory, endocrinological or neurological factors; of these, circulatory disturbance has been estimated to be the most significant, because erectile function is physiological and directly depends on blood circulation. Thus ED and cardiovascular disease share risk factors [12,13] and pathological changes in the cavernosal tissue of patients with ED are similar to those in the vascular wall in patients with atherosclerosis . Through studies of the relationship between ED and circularity disease, a strong association between these disorders has been widely recognized. Furthermore, some authors report that ED is a reliable marker of coronary heart disease . In the present study penile cavernosal arterial blood flow correlated significantly with retinal vascular conditions, suggesting that arteriogenic ED is also a target-organ disease of atherosclerosis, and supporting previous reports of the relationship between ED and cardiovascular diseases.
The onset of atherosclerosis is not simultaneous in all organs; there is an order in its progression  and many consider that this characteristic is important, because if the damage to any one organ is known, damage to the next can be predicted [2,16,17]. Thus the retinal condition is thought to be a predictor of ischaemic heart disease . The present significant relation between cavernosal arterial PSV and retinal grade suggests therefore that arteriogenic ED might also be a predictor of ischaemic heart disease. Relationships between the degree of coronary arterial disease  and erectile function, and between cavernosal arterial blood flow and ischaemic heart disease, have been reported . When treating arteriogenic ED, attention should be given not only to the existing cardiovascular condition but also to the possibility of subsequent cardiovascular disease.
Cigarette smoking is considered to be one of the risk factors in atherosclerosis  but in the present study it was not a significant factor in cavernosal or fundus artery findings. The difficulty in measuring the exposure to cigarette smoking might have influenced this result. Hypertension is also considered a risk factor in atherosclerosis  but again it was not a significant factor for retinal findings or cavernosal arterial condition. This is probably because no patients had untreated hypertension and all those with a history of hypertension had their blood pressure adequately controlled. The present results agree with those where well-controlled hypertension was not a risk factor in ED .
To date, examining the fundus has not been important in assessing patients with ED; the present evaluation was only considered when assessing phosphodiesterase in the retina and retinitis pigmentosa at the time of prescribing sildenafil citrate [23,24]. While the diagnosis of this relatively rare hereditary disease is important, the main clinical value of fundoscopy is to reveal the systemic vascular condition of the patients. At present, primary physicians are important in treating ED; in many instances, while the primary physician cannot diagnose the detailed causes of ED, they can use fundoscopy, by which they can assess not only any atherosclerosis but also predict the condition of the penile cavernosal arteries. If a patient has normal fundi his complaint of ED might not be ‘common arteriogenic ED’ but one that should be treated with specific methods, including hormonal therapy, psychotherapy or penile revascularization.