KCN is characterized by a asymmetrical bilateral central or paracentral corneal stromal thinning, leading to alteration in the corneal curvature. In the initial stage, KCN may be asymptomatic, but its progression causes visual morbidity due to high astigmatism and anisometropia. Patients with KCN usually complains about decreased visual acuity, which could not be improved after correcting the refrative error[11, 12].
Diagnosis of KCN, even in the initial stage, is feasiblly available with specific methods, such as corneal topography, corneal tomography, Holladay map display, and Belin/Ambrosio Enhanced Ectasia Display[13-15]. In paritcular, high astigmatism or an asymmetrical bowtie pattern deteced in corneal topography maps are clinically suggestive of KCN[16, 17]. Different patterns of astigmatism would lead to asymmetrical bowtie pattern with different shapes, such as superior steep, inferior steep, round or oval. All these patterns indicate corneal ectatic disorders. As in our case, the corneal topgraphy reveals an asymmetrical bowtie patterns in the left eye, which is inferior steepening. The refractive error of high mypia and high astigmatism in the left eye lead to an unimproved visual acuity. Thus, the left eye is definitely diagnozed as KCN. As for the right eye, we found that the refractive error is much lower than that of the left eye and the BCVA is 1.0 even though there is also an asymmetrical bowtie patterns in corneal topography maps. The reason might be that the KCN of the right eye is in its early stageand the central point of cornea could still retains intact corneal curvature after correcting the refractive error. Therefore, the right eye should also be diagnozed as KCN. The anisometropia between the right and left eye of our case, to some exent, demontrates the phenomena of asymmetrical bilateral progression of KCN.
Decreased vision, which could not be improved by correcting the refractive error is usually associated with lesion in the posterior segment of the eye, such as retinal diseases, macular diseases, optic nerve diseases. Progress in ocular imaging techniques, particular OCT and FFA, allows high-resolution observation of subtle morphological changes of the retina. However, as the lesion of KCN lies in the cornea, no pathologic changes would be found in the posterior segment by fundus picture, OCT, FFA or ICGA, unless other systemic diseases accompany. In the present case, we do not get positive clues from all the above examinations. In the first begining, we did not bring about KCN as the reason for the unimproved visioin acuity, as we did not find obvious changes of the cornea under slit-lamp. Commonly, electrophysiological tests might be of great usefulness in hinting on the position of lesion in case of unknown reasons for the decreased visual acuity or unimproved visual acuity[9, 10]. Fortunately, we got the hint of lesion location after analyzing the combined results of eletrophysiological investigations, i.e. ffERG, PVEP and FEVP.
ffERG is a mass potential of the summed electrical activity of the retina, which evaluats the global retinal function reflecting the whole retinal function. The influence of ocular media would not be so impressive as the stimuli for ffERG is a series of flash, unless the opaque media is so severe that it reduces the flash strength reaching the retina. In this condition, the Dark-adapted 10 ERG of ISCEV ffERG may give more reliable responses in patients with opaque media, as the strong flash strength is as strong as 10 photopic cd s m-2. In our case, the ERG parameters did not reveal obvious abnormaility in both dark-adapted and light-adapted ERG, in both a-wave and b-wave, indicating the global function of outer and middle layer of retina is intact. Our OCT scaning along with the FFA and ICGA could in some extent exclude the possibility of lesion in macula although we do not perform multifocus (mf) ERG to provide a topographic measure of electrophysiological activity for macula.
VEP, recorded from the overlying scalp, are visually evoked electrophysiological signals in the visual cortex that extract from the electroencephalographic activity. Normal VEP waveforms rely on the functional integrity of central vision at all levels of the visual pathway, as visual cortex is activated primarily by the central visual field. PVEP, getting the waveform with the pattern-reversal checkboard stimuli, is less variable in waveform and timing than the VEP elicited by other stimuli. In great details, P100 is usually a prominent peak that shows relatively little variation between subjects, minimal within-subject interocular difference, and minimal variation with repeated measurements over time. Herein, PVEP has been very popular in clinic. Usually, abnormalities of PVEP parameter, particular the latency of P100, are associated with optic nerve diseases when patients get an unimproved visual acuity[24, 25]. We found reduced amplitude and delayed latency of P100-wave in both eyes in the present case. We first assumed that the lesion might lie in the optic never or the pathway latter. However, peak time of P100 is affected by nonpathophysiologic parameters such as refractive error, ocular media, poor fixation. The reduced amplitude in PVEP might be cuased by the the light scatter from the irregular astigmatism, as light scatter has an effect on the mfERG amplitudes. In addition, Geng, W. J. et al. reported that PVEP is susceptible to the influence of visual attention. Thus, PVEP data alone could not ensure whether the lesion lies in the ocular media or on the posterior segment.
FVEP, which are more variable than PVEP across typical subjects, usually remain similar between eyes of an individual subject. Patients who are unable or unwilling to cooperate for PVEP, or with optical factors, such as media opacities, that prevent the valid use of pattern stimuli, FVEP can give useful clinical information to complement that available from PVEP. Usually, the most consistent and robust components in FVEP from typical adults are the P2 peaks. In our case, the latency and amplitude of P2-wave in both eyes are comparable. In addition, there parameters are all within normative ranges.
The abnormal PVEP parameters and the normal FVEP parameters lead us to focus the lesion on the on the ocular media. We confirmed the abnormality of PVEP by asking the patient to count the times of pattern reversal as to focus his attention. In addition, we excluded the possibility of malingering as the reason for the unimproved VA. Furthermore, the ocular media of the patient including the anterior chamber, the lens and the vitreal body, are clear in general. Considering the above situations, we assumed that the lesion might happened in the cornea, which lead us to come up with the ideal of KCN and was finally confirmed a by corneal topography, as noted before.
KCN, commonly arising as an isolated disorder, might also be associated with systemic disease, such as Down’s syndrome and Turner’s syndrome [29, 30]. In some cases, KCN may be accompanied by other ocular disorders, such macular dysfunction, retinitis pigmentosa, Leber’s congenital amaurosis. Usually in this case, eletroretinographic tests are of great use in evaluating potential diseases, especially when visualization of the posterior segment might not be visible ophthalmoscopically due to the high refractive error and the corneal opacities. There are several reports that KCN is accompanied by other diseases found by ERG or VEP. Moschos et al. reported that the retinal response density in mf-ERG differed significantly between some KCN patients and controls, implying that impaired macular function might coexist in some KCN patients. They also applied ERG and VEP in a series of 233 KCN patients and revealed the existence of a diffuse tapetoretinal degeneration or a macular lesion in many cases. Nguyen, D. Q. et al. diagnosed a 35-year-old male of KCN associated with congenital stationary night blindness type 1, whose ERG recording revealed no response to the dim flash in the dark and a “negative” waveform to the standard flash with near absence of b-wave. In such circumstances, the low visual acuity of these KCN might not only be attributed to the corneal abnormality, but also to the retinal dysfunction. Furthermore, the preoperative electrophysiological studies of such KCN cases could provide valuable prognostic information and are crucial to avoid a needless treatment, such as corneal transplantation. Fogla, R. et al. discovered an unimproved BCVA after uneventful penetrating keratoplasty in the left eye of a bilateral KCN case, whose postoperative ERG results indicated the coexistence of cone-rod dystrophy. Actually, we do not find any significant dysfunction of retinal function and the visual pathway through ERG and VEP in our case. Thus, we could predict in some extent that the patient could gain a good vision quality after successful treatment in the cornea.
In summary, we present the diagnostic process of a case of KCN after the hint of lesion location by electrophysiological studies in combined with other morphological examinations. The availability of electrophysiology could help to gain a deeper understanding of clinical picture and prognostic outcome of treatment for KCN. In addition, KCN should be suspected in any patient with significant irregular stigmatism, especially if unstable and increasing over time and when no obvious lesion exists in other parts of the eye.